Recurrent spontaneous abortion (RSA) is a complex and heterogeneous disorder with multiple etiologies. Genetic factors are thought to play an important role in the etiology of RSA. With recent advances in genetic test...Recurrent spontaneous abortion (RSA) is a complex and heterogeneous disorder with multiple etiologies. Genetic factors are thought to play an important role in the etiology of RSA. With recent advances in genetic testing technologies, there has been an increasing interest in using these tools to diagnose the etiology of RSA. This review discusses the different types of genetic testing methods, such as karyotyping, chromosomal microarray analysis, next-generation sequencing, and their applications in the diagnosis of the etiology RSA. The use of genetic testing in the diagnosis of RSA has the potential to improve the accuracy of diagnosis and the understanding of the underlying mechanisms of the disorder, which could lead to better management and treatment of affected individuals.展开更多
BACKGROUND Several genetic testing techniques have been recommended as a first-tier diagnostic tool in clinical practice for diagnosing autism spectrum disorder(ASD).However,the actual usage rate varies dramatically.T...BACKGROUND Several genetic testing techniques have been recommended as a first-tier diagnostic tool in clinical practice for diagnosing autism spectrum disorder(ASD).However,the actual usage rate varies dramatically.This is due to various reasons,including knowledge and attitudes of caregivers,patients,and health providers toward genetic testing.Several studies have therefore been conducted worldwide to investigate the knowledge,experiences,and attitudes toward genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers who provide medical services for them.However,no systematic review has been done.AIM To systematically review research on knowledge,experiences,and attitudes towards genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers.METHODS We followed the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines and searched the literature in three English language databases(PubMed,Web of Science,and PsychInfo)and two Chinese databases(CNKI and Wanfang).Searched literature was screened independently by two reviewers and discussed when inconsistency existed.Information on characteristics of the study,characteristics of participants,and main findings regarding knowledge,experience,and attitudes of caregivers of children with ASD,adolescent and adult ASD patients,and health providers concerning ASD genetic testing were extracted from included papers into a charting form for analysis.RESULTS We included 30 studies published between 2012 and 2022 and conducted in 9 countries.Most of the studies(n=29)investigated caregivers of children with ASD,one study also included adolescent and adult patients,and two covered health providers.Most(51.0%-100%)of the caregivers/patients knew there was a genetic cause for ASD and 17.0%to 78.1%were aware of ASD genetic testing.However,they lacked full understanding of genetic testing.They acquired relevant and necessary information from physicians,the internet,ASD organizations,and other caregivers.Between 9.1%to 72.7%of caregivers in different studies were referred for genetic testing,and between 17.4%to 61.7%actually obtained genetic testing.Most caregivers agreed there are potential benefits following genetic testing,including benefits for children,families,and others.However,two studies compared perceived pre-test and post-test benefits with conflicting findings.Caregivers concerns included high costs,unhelpful results,negative influences(e.g.,causing family conflicts,causing stress/risk/pain to children etc.)prevented some caregivers from using genetic testing.Nevertheless,46.7%to 95.0%caregivers without previous genetic testing experience intended to obtain it in the future,and 50.5%to 59.6%of parents previously obtaining genetic testing would recommend it to other parents.In a single study of child and adolescent psychiatrists,54.9%of respondents had ordered ASD genetic testing for their patients in the prior 12 mo,which was associated with greater knowledge of genetic testing.CONCLUSION Most caregivers are willing to learn about and use genetic testing.However,the review showed their current knowledge is limited and usage rates varied widely in different studies.展开更多
Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous ...Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.展开更多
Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in Chin...Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.展开更多
BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH childr...BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH children,genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence.CASE SUMMARY We report a case of CAH with a high suspicion before delivery.The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results.Our report confirmed a CYP21A2 homozygous deletion in this case,CYP21A2 heterozygous deletion in the mother,and a rare 2+0 CYP21A2 deletion in the father.CONCLUSION It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.展开更多
Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited cardiomyopathies.As novel mutations have been identified,understanding when to ...Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited cardiomyopathies.As novel mutations have been identified,understanding when to consider genetic testing has emerged as an important consideration in the management of these cases.Specific genetic testing has a paramount importance in the risk stratification of family members,in the prognosis of probands at higher risk of a serious phenotype expression,and finally in the identification of new mutations,all of which are discussed in this review.The indications for each type of cardiomyopathy are described,along with the limitations of genetic testing.Finally,the importance of public sharing of variants in large data sets is emphasized.The ultimate aim of this review is to present key messages about the genetic testing process in order to minimize potential harms and provide suggestions to specialized clinicians who act as a part of a multidisciplinary team in order to offer the best care to families with inherited cardiomyopathies.展开更多
BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple gen...BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.展开更多
BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically...BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically addressing the psychological adjustment of people with inconclusive results are scarce.AIM To examine psychological outcomes of receiving an uninformative BRCA1/2 test result.METHODS PubMed,PsychInfo,and Cochrane Central Register of Controlled Trials were screened for studies focusing on distress,anxiety,and depression levels in individuals with inconclusive genetic test results.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS Studies on psychological outcomes of inconclusive BRCA1/2 focused on general and specific distress,anxiety,and depression.Overall,they produced mixed results.These inconsistent findings are probably due to the uncertainty caused by this type of result,that may also influence the decisions of individuals about surveillance and prophylactic options,reducing their compliance.In addition,this review highlights specific risk and protective factors that affect psychological adjustment in individuals with an inconclusive genetic testing result.CONCLUSION Individuals with inconclusive genetic test results need specific educational programs and support to better understand the meaning of their results in order to be able to make decisions about surveillance and prophylactic options.展开更多
Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different ...Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.展开更多
In Pakistan which ranked second in terms of hepatitis C virus(HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy responseprediction. Interleukin 28B(IL-28B) genetic testin...In Pakistan which ranked second in terms of hepatitis C virus(HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy responseprediction. Interleukin 28B(IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28 B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security(health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28 B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients.展开更多
Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the onco...Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the oncosuppressor gene MEN1, in 1997, genetic testing has revealed an important approach for the early and differential diagnosis of the disease. The finding of a MEN1 mutation in a patient has important clinical implications for relatives since it allows very early disease diagnosis and identification of carriers, even before biochemical and/or clinical manifestation, permitting their inclusion in a specific program of surveillance and subsequent praecox therapy. Currently, genetic testing for MEN1 consists principally of the sequencing of coding regions and intron-exon junctions of the MEN1 gene. However, the recent acquisition of novel high throughput technologies will allow the design of innovative, accurate, complete and rapid genetic diagnosis. These new tools are able to increase the strength of the analysis and almost completely eliminate the possibility of false negative results. This review aims to give an overview on genetic testing of MEN1 syndrome, reporting the positive aspects of performing the analysis and the future perspectives for improving the performance of the test, as well as its application in clinical practice.展开更多
BACKGROUND Carcinoembryonic antigen(CEA)and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms.Genetic testing and microforceps biopsy are promising tools for pre-operativ...BACKGROUND Carcinoembryonic antigen(CEA)and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms.Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.METHODS We performed a literature search in Medline,Scopus,and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts,with endoscopic ultrasound with fine-needle aspiration(EUSFNA)prior to surgery and surgical pathology as reference standard for diagnosis.We evaluated the diagnostic accuracy for:1-benign cysts;2-mucinous low-risk cysts;3-high-risk cysts,and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis.We also assessed publication bias,heterogeneity,and study quality.RESULTS Eight studies,including 1206 patients,of which 203(17%)referred for surgery who met the inclusion criteria were analyzed in the systematic review,and seven studies were included in the meta-analysis.Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts.Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts,with sensitivities of 0.89(95%CI:0.79-0.95)and 0.57(95%CI:0.42-0.71),specificities of 0.88(95%CI:0.75-0.95)and 0.88(95%CI:0.80-0.93)and AUC of 0.9555 and 0.92,respectively.The diagnostic yield was higher in microforceps biopsies than in genetic analysis(0.73 vs 0.54,respectively)but the rates of correctly identified cysts were identical(0.73 with 95%CI:0.62-0.82 vs 0.71 with 95%CI:0.49-0.86,respectively).CONCLUSION Genetic testing and microforceps biopsies are useful second tests,with identical results in benign pancreatic cysts.Genetic analysis performs better for low-and high-risk cysts but has lower diagnostic yield.展开更多
Clinical testing of patients for hereditary breast and ovarian cancer syndromes began in the mid-1990s with the identification of the BRCA1 and BRCA2 genes.Since then,mutations in dozens of other genes have been corre...Clinical testing of patients for hereditary breast and ovarian cancer syndromes began in the mid-1990s with the identification of the BRCA1 and BRCA2 genes.Since then,mutations in dozens of other genes have been correlated to increased breast,ovarian,and other cancer risk.The following decades of data collection and patient advocacy allowed for improvements in medical,legal,social,and ethical advances in genetic testing.Technological advances have made it possible to sequence multiple genes at once in a panel to give patients a more thorough evaluation of their personal cancer risk.Panel testing increases the detection of mutations that lead to increased risk of breast,ovarian,and other cancers and can better guide individualized screening measures compared to limited BRCA testing alone.At the same time,multi-gene panel testing is more time-and cost-efficient.While the clinical application of panel testing is in its infancy,many problems arise such as lack of guidelines for management of newly identified gene mutations,high rates of variants of uncertain significance,and limited ability to screen for some cancers.Through on-going concerted efforts of pooled data collection and analysis,it is likely that the benefits of multi-gene panel testing will outweigh the risks in the near future.展开更多
Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of he...Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.展开更多
Inherited cardiomyopathies are major causes of morbidity and mortality and include a group of cardiac disorders such as hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy,arrhythmogenic right ventricular dysplasi...Inherited cardiomyopathies are major causes of morbidity and mortality and include a group of cardiac disorders such as hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy,arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C),left ventricular noncompaction(LVNC),and restrictive cardiomyopathy(RCM).These diseases have a substantial genetic component and predispose to sudden cardiac death.Since the first gene was identified as a disease-causing gene for HCM over two decades ago,more than eighty genes have been identified to be associated with inherited cardiomyopathies and genetic testing has become prevalent in making clinical diagnosis.With the advent of next-generation sequencing technology,genetic panel testing of inherited cardiomyopathies has become feasible and cost efficient.In this review,we summarize the individual cardiomyopathies with the emphasis on cardiomyopathy genetics and genetic testing.展开更多
BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enz...BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.展开更多
Next generations sequencing (NGS) is definitely one of the most revolutionary technology of the last years in genetic and medical field (Kricka and Di Resta, 2013). It brought important changes in genetic testing of i...Next generations sequencing (NGS) is definitely one of the most revolutionary technology of the last years in genetic and medical field (Kricka and Di Resta, 2013). It brought important changes in genetic testing of inherited human disorders, in particular in neurological Mendelian forms, such as inherited neuropathies, ataxias or monogenic form of epilepsy, where “diagnostic odyssey” is quite common.展开更多
Purpose: This study aimed to characterize mood and quality of life and to examine the associations of these areas with subjective cognitive concerns and attitudes toward genetic testing for the Common Hispanic Mutatio...Purpose: This study aimed to characterize mood and quality of life and to examine the associations of these areas with subjective cognitive concerns and attitudes toward genetic testing for the Common Hispanic Mutation, a gene that has been associated with increased risk for CCM1. Method: Fifty-four adults with previous genetic testing for the Common Hispanic Mutation completed a mail survey that included assessments of the above identified areas. Results: Self-reported depressive symptoms and quality of life did not differ between those with positive and negative genetic test results. The negative group expressed a more favorable attitude toward genetic testing (p p = 0.06). Using generalized linear regression, more subjective cognitive concerns were associated with poorer quality of life and more depressive symptoms (p p Conclusions: Subjective cognitive concerns and negative attitudes toward genetic testing may influence emotional well-being after genetic testing for the Common Hispanic Mutation. Additional research is needed that uses objective neuropsychological measures to understand the associations of subjective cognitive concerns, emotional well-being, and cognitive test performance in individuals with CCM1. There is also a need for research that focuses on protective factors and resiliency following genetic testing for CCM1 and the development of mental health interventions to preempt psychosocial difficulties.展开更多
Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus...Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus.Originally used for early onset monogenic conditions,PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology,assisted reproductive techniques(ARTs),and in vitro fertilization(IVF).This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test,with a particular focus on the current challenges related to laws,ethics,counseling,and technology.Additionally,this review predicts the future potential applications of this method.Although PGT may be utilized to predict and prevent hereditary cancer,each case should be comprehensively evaluated.The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes,and non-pathogenic phenotypes must be carefully evaluated.Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning.PGT may be the preferred treatment for hereditary cancer cases;however,such cases require careful case-by-case evaluations.Therefore,this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.展开更多
The first practice of pre-implantation genetic testing(PGT)was reported more than 30 years ago.PGT,originally named preimplantation genetic screening(PGS)and pre-implantation genetic diagnosis(PGD),is now categorized ...The first practice of pre-implantation genetic testing(PGT)was reported more than 30 years ago.PGT,originally named preimplantation genetic screening(PGS)and pre-implantation genetic diagnosis(PGD),is now categorized as PGT for aneuploidies(PGT-A),PGT for monogenic/single-gene defects(PGT-M),and PGT for chromosomal structural rearrangements(PGT-SR).Patients with fertility issues caused by advanced maternal age,carrier status of chromosomal abnormalities,or harboring pathogenic variant(s)are recommended to undergo PGT to increase the possibility of successful live birth and avoid potentially affected newborns.High-throughput techniques,such as DNA microarrays and next-generation sequencing(NGS),have enabled comprehensive screening of all 24 chromosomes,instead of few loci at a time.Furthermore,as a comprehensive PGT,PGT-Plus was enabled by the rapid development of a genome-wide single-cell haplotyping technique to detect embryo aneuploidy,single-gene disorders,and chromosomal aberrations simultaneously using a single universal protocol.In addition,non-invasive approaches enable a more intact embryo during the biopsy procedure,which may avoid potential mosaicism issues at a certain scale by testing spent culture media(SCM).As a novel PGT application,PGT-P detects genome-wide variations in polygenic diseases,which account for a large proportion of premature human deaths and affect a markedly larger population than monogenic diseases,using polygenic risk score calculation to decrease the potential of affecting complex conditions.Owing to the emergence of new technologies recruited to PGTs,more couples with infertility issues have a promising chance of conceiving a healthy baby,ultimately facilitating the human species to live more prosper.展开更多
文摘Recurrent spontaneous abortion (RSA) is a complex and heterogeneous disorder with multiple etiologies. Genetic factors are thought to play an important role in the etiology of RSA. With recent advances in genetic testing technologies, there has been an increasing interest in using these tools to diagnose the etiology of RSA. This review discusses the different types of genetic testing methods, such as karyotyping, chromosomal microarray analysis, next-generation sequencing, and their applications in the diagnosis of the etiology RSA. The use of genetic testing in the diagnosis of RSA has the potential to improve the accuracy of diagnosis and the understanding of the underlying mechanisms of the disorder, which could lead to better management and treatment of affected individuals.
基金the National Natural Science Foundation of China,No.81920108018(Li T and Sham P),No.82001409(Zhang YM)the Key R&D Program of Zhejiang,No.2022C03096(Li T)Project for Hangzhou Medical Disciplines of Excellence。
文摘BACKGROUND Several genetic testing techniques have been recommended as a first-tier diagnostic tool in clinical practice for diagnosing autism spectrum disorder(ASD).However,the actual usage rate varies dramatically.This is due to various reasons,including knowledge and attitudes of caregivers,patients,and health providers toward genetic testing.Several studies have therefore been conducted worldwide to investigate the knowledge,experiences,and attitudes toward genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers who provide medical services for them.However,no systematic review has been done.AIM To systematically review research on knowledge,experiences,and attitudes towards genetic testing among caregivers of children with ASD,adolescent and adult ASD patients,and health providers.METHODS We followed the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines and searched the literature in three English language databases(PubMed,Web of Science,and PsychInfo)and two Chinese databases(CNKI and Wanfang).Searched literature was screened independently by two reviewers and discussed when inconsistency existed.Information on characteristics of the study,characteristics of participants,and main findings regarding knowledge,experience,and attitudes of caregivers of children with ASD,adolescent and adult ASD patients,and health providers concerning ASD genetic testing were extracted from included papers into a charting form for analysis.RESULTS We included 30 studies published between 2012 and 2022 and conducted in 9 countries.Most of the studies(n=29)investigated caregivers of children with ASD,one study also included adolescent and adult patients,and two covered health providers.Most(51.0%-100%)of the caregivers/patients knew there was a genetic cause for ASD and 17.0%to 78.1%were aware of ASD genetic testing.However,they lacked full understanding of genetic testing.They acquired relevant and necessary information from physicians,the internet,ASD organizations,and other caregivers.Between 9.1%to 72.7%of caregivers in different studies were referred for genetic testing,and between 17.4%to 61.7%actually obtained genetic testing.Most caregivers agreed there are potential benefits following genetic testing,including benefits for children,families,and others.However,two studies compared perceived pre-test and post-test benefits with conflicting findings.Caregivers concerns included high costs,unhelpful results,negative influences(e.g.,causing family conflicts,causing stress/risk/pain to children etc.)prevented some caregivers from using genetic testing.Nevertheless,46.7%to 95.0%caregivers without previous genetic testing experience intended to obtain it in the future,and 50.5%to 59.6%of parents previously obtaining genetic testing would recommend it to other parents.In a single study of child and adolescent psychiatrists,54.9%of respondents had ordered ASD genetic testing for their patients in the prior 12 mo,which was associated with greater knowledge of genetic testing.CONCLUSION Most caregivers are willing to learn about and use genetic testing.However,the review showed their current knowledge is limited and usage rates varied widely in different studies.
文摘Next generation sequencing is currently a cornerstone of genetic testing in routine diagnostics,allowing for the detection of sequence variants with so far unprecedented large scale,mainly in genetically heterogenous diseases,such as neurological disorders.It is a fast-moving field,where new wet enrichment protocols and bioinformatics tools are constantly being developed to overcome initial limitations.Despite the as yet undiscussed advantages,however,there are still some challenges in data analysis and the interpretation of variants.In this review,we address the current state of next generation sequencing diagnostic testing for inherited human disorders,particularly giving an overview of the available high-throughput sequencing approaches;including targeted,whole-exome and whole-genome sequencing;and discussing the main critical aspects of the bioinformatic process,from raw data analysis to molecular diagnosis.
文摘Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.
基金Supported by the Fundamental Research Funds of Health Commission of Sichuan Province,No.17ZD035.
文摘BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH children,genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence.CASE SUMMARY We report a case of CAH with a high suspicion before delivery.The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results.Our report confirmed a CYP21A2 homozygous deletion in this case,CYP21A2 heterozygous deletion in the mother,and a rare 2+0 CYP21A2 deletion in the father.CONCLUSION It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.
文摘Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited cardiomyopathies.As novel mutations have been identified,understanding when to consider genetic testing has emerged as an important consideration in the management of these cases.Specific genetic testing has a paramount importance in the risk stratification of family members,in the prognosis of probands at higher risk of a serious phenotype expression,and finally in the identification of new mutations,all of which are discussed in this review.The indications for each type of cardiomyopathy are described,along with the limitations of genetic testing.Finally,the importance of public sharing of variants in large data sets is emphasized.The ultimate aim of this review is to present key messages about the genetic testing process in order to minimize potential harms and provide suggestions to specialized clinicians who act as a part of a multidisciplinary team in order to offer the best care to families with inherited cardiomyopathies.
文摘BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at once.Here,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-M)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)couple.CASE SUMMARY A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling.They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)genotype.Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both parents.The couple requested in vitro fertilization(IVF)and PGT-M for PA.From IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality embryos.Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid.Endpoint polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo.Both embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn screening.CONCLUSION We show that using PGT-M with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.
文摘BACKGROUND An inconclusive result from BRCA1/2 genetic testing indicates that a genetic variant of uncertain significance is detected.This case constitutes the majority of genetic test results,but studies specifically addressing the psychological adjustment of people with inconclusive results are scarce.AIM To examine psychological outcomes of receiving an uninformative BRCA1/2 test result.METHODS PubMed,PsychInfo,and Cochrane Central Register of Controlled Trials were screened for studies focusing on distress,anxiety,and depression levels in individuals with inconclusive genetic test results.This review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method.RESULTS Studies on psychological outcomes of inconclusive BRCA1/2 focused on general and specific distress,anxiety,and depression.Overall,they produced mixed results.These inconsistent findings are probably due to the uncertainty caused by this type of result,that may also influence the decisions of individuals about surveillance and prophylactic options,reducing their compliance.In addition,this review highlights specific risk and protective factors that affect psychological adjustment in individuals with an inconclusive genetic testing result.CONCLUSION Individuals with inconclusive genetic test results need specific educational programs and support to better understand the meaning of their results in order to be able to make decisions about surveillance and prophylactic options.
基金Supported by A Canada research chair in electrophysiology and adult congenital heart disease(Paul Khairy)
文摘Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.
文摘In Pakistan which ranked second in terms of hepatitis C virus(HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy responseprediction. Interleukin 28B(IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28 B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security(health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28 B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients.
文摘Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant inherited tumour syndrome expressing various endocrine and non-endocrine lesions and tumours. Since the identification of the causative gene, the oncosuppressor gene MEN1, in 1997, genetic testing has revealed an important approach for the early and differential diagnosis of the disease. The finding of a MEN1 mutation in a patient has important clinical implications for relatives since it allows very early disease diagnosis and identification of carriers, even before biochemical and/or clinical manifestation, permitting their inclusion in a specific program of surveillance and subsequent praecox therapy. Currently, genetic testing for MEN1 consists principally of the sequencing of coding regions and intron-exon junctions of the MEN1 gene. However, the recent acquisition of novel high throughput technologies will allow the design of innovative, accurate, complete and rapid genetic diagnosis. These new tools are able to increase the strength of the analysis and almost completely eliminate the possibility of false negative results. This review aims to give an overview on genetic testing of MEN1 syndrome, reporting the positive aspects of performing the analysis and the future perspectives for improving the performance of the test, as well as its application in clinical practice.
文摘BACKGROUND Carcinoembryonic antigen(CEA)and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms.Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.METHODS We performed a literature search in Medline,Scopus,and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts,with endoscopic ultrasound with fine-needle aspiration(EUSFNA)prior to surgery and surgical pathology as reference standard for diagnosis.We evaluated the diagnostic accuracy for:1-benign cysts;2-mucinous low-risk cysts;3-high-risk cysts,and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis.We also assessed publication bias,heterogeneity,and study quality.RESULTS Eight studies,including 1206 patients,of which 203(17%)referred for surgery who met the inclusion criteria were analyzed in the systematic review,and seven studies were included in the meta-analysis.Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts.Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts,with sensitivities of 0.89(95%CI:0.79-0.95)and 0.57(95%CI:0.42-0.71),specificities of 0.88(95%CI:0.75-0.95)and 0.88(95%CI:0.80-0.93)and AUC of 0.9555 and 0.92,respectively.The diagnostic yield was higher in microforceps biopsies than in genetic analysis(0.73 vs 0.54,respectively)but the rates of correctly identified cysts were identical(0.73 with 95%CI:0.62-0.82 vs 0.71 with 95%CI:0.49-0.86,respectively).CONCLUSION Genetic testing and microforceps biopsies are useful second tests,with identical results in benign pancreatic cysts.Genetic analysis performs better for low-and high-risk cysts but has lower diagnostic yield.
文摘Clinical testing of patients for hereditary breast and ovarian cancer syndromes began in the mid-1990s with the identification of the BRCA1 and BRCA2 genes.Since then,mutations in dozens of other genes have been correlated to increased breast,ovarian,and other cancer risk.The following decades of data collection and patient advocacy allowed for improvements in medical,legal,social,and ethical advances in genetic testing.Technological advances have made it possible to sequence multiple genes at once in a panel to give patients a more thorough evaluation of their personal cancer risk.Panel testing increases the detection of mutations that lead to increased risk of breast,ovarian,and other cancers and can better guide individualized screening measures compared to limited BRCA testing alone.At the same time,multi-gene panel testing is more time-and cost-efficient.While the clinical application of panel testing is in its infancy,many problems arise such as lack of guidelines for management of newly identified gene mutations,high rates of variants of uncertain significance,and limited ability to screen for some cancers.Through on-going concerted efforts of pooled data collection and analysis,it is likely that the benefits of multi-gene panel testing will outweigh the risks in the near future.
基金the R01 grant from NIH/NIGMS and NIH/NIDCD(R01 DC016038,R01 DC017846)to Shuman HeR01 grants from NIH/NIDCD(R01 DC005575,R01 DC012115,and R01DC017264)to Xuezhong Liu.
文摘Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.
文摘Inherited cardiomyopathies are major causes of morbidity and mortality and include a group of cardiac disorders such as hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy,arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/C),left ventricular noncompaction(LVNC),and restrictive cardiomyopathy(RCM).These diseases have a substantial genetic component and predispose to sudden cardiac death.Since the first gene was identified as a disease-causing gene for HCM over two decades ago,more than eighty genes have been identified to be associated with inherited cardiomyopathies and genetic testing has become prevalent in making clinical diagnosis.With the advent of next-generation sequencing technology,genetic panel testing of inherited cardiomyopathies has become feasible and cost efficient.In this review,we summarize the individual cardiomyopathies with the emphasis on cardiomyopathy genetics and genetic testing.
基金Supported by Zhejiang Province Medical Science and Technology Project,No.2020RC061 and No.2019ZD021Jinhua Bureau of Science and Technology Project,No.2020-3-004.
文摘BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.
文摘Next generations sequencing (NGS) is definitely one of the most revolutionary technology of the last years in genetic and medical field (Kricka and Di Resta, 2013). It brought important changes in genetic testing of inherited human disorders, in particular in neurological Mendelian forms, such as inherited neuropathies, ataxias or monogenic form of epilepsy, where “diagnostic odyssey” is quite common.
文摘Purpose: This study aimed to characterize mood and quality of life and to examine the associations of these areas with subjective cognitive concerns and attitudes toward genetic testing for the Common Hispanic Mutation, a gene that has been associated with increased risk for CCM1. Method: Fifty-four adults with previous genetic testing for the Common Hispanic Mutation completed a mail survey that included assessments of the above identified areas. Results: Self-reported depressive symptoms and quality of life did not differ between those with positive and negative genetic test results. The negative group expressed a more favorable attitude toward genetic testing (p p = 0.06). Using generalized linear regression, more subjective cognitive concerns were associated with poorer quality of life and more depressive symptoms (p p Conclusions: Subjective cognitive concerns and negative attitudes toward genetic testing may influence emotional well-being after genetic testing for the Common Hispanic Mutation. Additional research is needed that uses objective neuropsychological measures to understand the associations of subjective cognitive concerns, emotional well-being, and cognitive test performance in individuals with CCM1. There is also a need for research that focuses on protective factors and resiliency following genetic testing for CCM1 and the development of mental health interventions to preempt psychosocial difficulties.
文摘Preimplantation genetic testing(PGT),which was developed as an alternative to prenatal genetic testing,allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus.Originally used for early onset monogenic conditions,PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology,assisted reproductive techniques(ARTs),and in vitro fertilization(IVF).This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test,with a particular focus on the current challenges related to laws,ethics,counseling,and technology.Additionally,this review predicts the future potential applications of this method.Although PGT may be utilized to predict and prevent hereditary cancer,each case should be comprehensively evaluated.The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes,and non-pathogenic phenotypes must be carefully evaluated.Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning.PGT may be the preferred treatment for hereditary cancer cases;however,such cases require careful case-by-case evaluations.Therefore,this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.
文摘The first practice of pre-implantation genetic testing(PGT)was reported more than 30 years ago.PGT,originally named preimplantation genetic screening(PGS)and pre-implantation genetic diagnosis(PGD),is now categorized as PGT for aneuploidies(PGT-A),PGT for monogenic/single-gene defects(PGT-M),and PGT for chromosomal structural rearrangements(PGT-SR).Patients with fertility issues caused by advanced maternal age,carrier status of chromosomal abnormalities,or harboring pathogenic variant(s)are recommended to undergo PGT to increase the possibility of successful live birth and avoid potentially affected newborns.High-throughput techniques,such as DNA microarrays and next-generation sequencing(NGS),have enabled comprehensive screening of all 24 chromosomes,instead of few loci at a time.Furthermore,as a comprehensive PGT,PGT-Plus was enabled by the rapid development of a genome-wide single-cell haplotyping technique to detect embryo aneuploidy,single-gene disorders,and chromosomal aberrations simultaneously using a single universal protocol.In addition,non-invasive approaches enable a more intact embryo during the biopsy procedure,which may avoid potential mosaicism issues at a certain scale by testing spent culture media(SCM).As a novel PGT application,PGT-P detects genome-wide variations in polygenic diseases,which account for a large proportion of premature human deaths and affect a markedly larger population than monogenic diseases,using polygenic risk score calculation to decrease the potential of affecting complex conditions.Owing to the emergence of new technologies recruited to PGTs,more couples with infertility issues have a promising chance of conceiving a healthy baby,ultimately facilitating the human species to live more prosper.
