The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turk...The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.展开更多
Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene.From a clinical perspective,LS patients exhi...Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene.From a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population.We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening protocols.Methods:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided.Results:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general population.LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary disorder.The current European Association of Urology(EAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset.Newly diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and gynecologists.Finally,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic alternative.Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial.Conclusion:Considering the strict association between UTUC and LS,we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm,including molecular evaluationandgenetic testing.To date,literature lacks clear evidence regarding the role of LS in developing bladder cancer,prostate cancer,or renal cell carcinoma,and current data are still inconclusive,highlighting the urgent need for further studies.展开更多
BACKGROUND Approximately 10%of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors.In the past,due to the limitations of detection technol...BACKGROUND Approximately 10%of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors.In the past,due to the limitations of detection technology and the nonspecific manifestations of uraemia,the etiological diagnosis is unclear.In addition to common monogenic diseases and complex disorders,advanced testing techniques have led to the recognition of more hereditary renal diseases.Here,we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests.CASE SUMMARY A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis.His father and paternal aunt both had a history of unexplained renal failure with haemodialysis,and his 10-year-old daughter presented with proteinuria.The patient had multiple congenital abnormalities,including bilateral overlapping toes,unilateral dysplastic external ears,and sensorineural hearing loss.His family members also presented with similar defects.Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2(c.3437delG),and Sanger sequencing confirmed the same mutation in all affected family members.CONCLUSION We report a novel SALL1 exon 2(c.3437delG)mutation and clinical syndrome with kidney disease,bilateral overlapping toes,unilateral dysplastic external ears,and sensorineural hearing loss in a four-generation Chinese family.展开更多
BACKGROUND Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life.They usually occur in the mediastinum or lung,but there are very rare cases of ectopic broncho...BACKGROUND Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life.They usually occur in the mediastinum or lung,but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity.A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen(CEA),harboring a GNAS mutation,is reported.The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts.CASE SUMMARY In 2007,a man in his 50s was incidentally found to have an intra-abdominal cystic mass,8 cm in diameter.Surgical resection was recommended,but he preferred to remain under observation.In 2020,his serum CEA level increased to 26.7 ng/mL,and abdominal computed tomography showed a 15 cm×12 cm,multifocal,cystic mass located predominantly on the lesser curvature of the stomach.Since malignancy could not be ruled out,he finally underwent surgical resection.Histologically,the cystic wall was lined by ciliated columnar epithelium,accompanied by bronchial gland-like tissue,bronchial cartilage,and smooth muscle.Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5%and positive for CEA.Moreover,a GNAS mutation(p.R201C)was detected in the atypical epithelium,leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm.The patient is currently undergoing outpatient follow-up without recurrence.CONCLUSION An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.展开更多
Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human diseas...Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human disease treatment.Cas9,by far the most extensively used gene-editing nuclease,has shown great promise for the treatment of hereditary diseases,viral infection,cancers,and so on.Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications.Despite the rapid progress in basic research and clinical tests,some underlying problems present continuous,significant challenges,such as editing efficiency,relative difficulty in delivery,off-target effects,immunogenicity,etc.This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development.CRISPR-Cas systems,as a powerful gene-editing approach,will offer great hopes in clinical treatments for many individuals with currently incurable diseases.展开更多
Backgrounds TypeⅠinterferonopathy is a group of autoinflammatory disorders associated with prominent enhanced typeⅠinterferon signaling.The mechanisms are complex,and the clinical phenotypes are diverse.This review ...Backgrounds TypeⅠinterferonopathy is a group of autoinflammatory disorders associated with prominent enhanced typeⅠinterferon signaling.The mechanisms are complex,and the clinical phenotypes are diverse.This review briefly summarized the recent progresses of typeⅠinterferonopathy focusing on the clinical and molecular features,pathogeneses,diagnoses and potential therapies.Data sources Original research articles and literature reviews published in PubMed-indexed journals.Results TypeⅠinterferonopathies include Aicardi-Goutières syndrome,spondyloenchondro-dysplasia with immune dysregulation,stimulator of interferon genes-associated vasculopathy with onset in infancy,X-linked reticulate pigmentary disorder,ubiquitin-specific peptidase 18 deficiency,chronic atypical neutrophilic dermatitis with lipodystrophy,and Singleton-Merten syndrome originally.Other disorders including interferon-stimulated gene 15 deficiency and DNAseⅡdeficiency are believed to be interferonopathies as well.Intracranial calcification,skin vasculopathy,interstitial lung disease,failure to thrive,skeletal development problems and autoimmune features are common.Abnormal responses to nucleic acid stimuli and defective regulation of protein degradation are main mechanisms in disease pathogenesis.First generation Janus kinase inhibitors including baricitinib,tofacitinib and ruxolitinib are useful for disease control.Reverse transcriptase inhibitors seem to be another option for Aicardi-Goutières syndrome.Conclusions Tremendous progress has been made for the discovery of typeⅠinterferonopathies and responsible genes.Janus kinase inhibitors and other agents have potential therapeutic roles.Future basic,translational and clinical studies towards disease monitoring and powerful therapies are warranted.展开更多
文摘The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.
文摘Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene.From a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population.We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening protocols.Methods:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided.Results:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general population.LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary disorder.The current European Association of Urology(EAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset.Newly diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and gynecologists.Finally,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic alternative.Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial.Conclusion:Considering the strict association between UTUC and LS,we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm,including molecular evaluationandgenetic testing.To date,literature lacks clear evidence regarding the role of LS in developing bladder cancer,prostate cancer,or renal cell carcinoma,and current data are still inconclusive,highlighting the urgent need for further studies.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LQ19H050003General Project Funds from the Health Department of Zhejiang Province,No.2020KY439.
文摘BACKGROUND Approximately 10%of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors.In the past,due to the limitations of detection technology and the nonspecific manifestations of uraemia,the etiological diagnosis is unclear.In addition to common monogenic diseases and complex disorders,advanced testing techniques have led to the recognition of more hereditary renal diseases.Here,we report a four-generation Chinese family in which four individuals had a novel SALL1 mutation and presented with uraemia or abnormal urine tests.CASE SUMMARY A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis.His father and paternal aunt both had a history of unexplained renal failure with haemodialysis,and his 10-year-old daughter presented with proteinuria.The patient had multiple congenital abnormalities,including bilateral overlapping toes,unilateral dysplastic external ears,and sensorineural hearing loss.His family members also presented with similar defects.Genetic testing revealed that the proband carried a novel heterozygous shift mutation in SALL1_exon 2(c.3437delG),and Sanger sequencing confirmed the same mutation in all affected family members.CONCLUSION We report a novel SALL1 exon 2(c.3437delG)mutation and clinical syndrome with kidney disease,bilateral overlapping toes,unilateral dysplastic external ears,and sensorineural hearing loss in a four-generation Chinese family.
文摘BACKGROUND Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life.They usually occur in the mediastinum or lung,but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity.A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen(CEA),harboring a GNAS mutation,is reported.The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts.CASE SUMMARY In 2007,a man in his 50s was incidentally found to have an intra-abdominal cystic mass,8 cm in diameter.Surgical resection was recommended,but he preferred to remain under observation.In 2020,his serum CEA level increased to 26.7 ng/mL,and abdominal computed tomography showed a 15 cm×12 cm,multifocal,cystic mass located predominantly on the lesser curvature of the stomach.Since malignancy could not be ruled out,he finally underwent surgical resection.Histologically,the cystic wall was lined by ciliated columnar epithelium,accompanied by bronchial gland-like tissue,bronchial cartilage,and smooth muscle.Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5%and positive for CEA.Moreover,a GNAS mutation(p.R201C)was detected in the atypical epithelium,leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm.The patient is currently undergoing outpatient follow-up without recurrence.CONCLUSION An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.
基金This work was supported by the National Institutes of Health(NIH)(Grant No.AI138203-3)the American Association of Immunologists through a Careers in Immunology Fellowship.This work was also supported by the National Natural Science Foundation of China(Grants No.82020108021 and 32000033).
文摘Clustered regularly interspaced short palindromic repeats(CRISPR)-associated systems(Cas)are efficient tools for targeting specific genes for laboratory research,agricultural engineering,biotechnology,and human disease treatment.Cas9,by far the most extensively used gene-editing nuclease,has shown great promise for the treatment of hereditary diseases,viral infection,cancers,and so on.Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications.Despite the rapid progress in basic research and clinical tests,some underlying problems present continuous,significant challenges,such as editing efficiency,relative difficulty in delivery,off-target effects,immunogenicity,etc.This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development.CRISPR-Cas systems,as a powerful gene-editing approach,will offer great hopes in clinical treatments for many individuals with currently incurable diseases.
基金This study was supported by funds from Public Welfare Scientific Research Project of China(201402012)CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses to HW(2016ZX310182-1)+1 种基金CAMS Innovation Fund for Medical Sciences(2016-I2M-1-008)The Capital Health Research and Development of Special(2016-2-40114).
文摘Backgrounds TypeⅠinterferonopathy is a group of autoinflammatory disorders associated with prominent enhanced typeⅠinterferon signaling.The mechanisms are complex,and the clinical phenotypes are diverse.This review briefly summarized the recent progresses of typeⅠinterferonopathy focusing on the clinical and molecular features,pathogeneses,diagnoses and potential therapies.Data sources Original research articles and literature reviews published in PubMed-indexed journals.Results TypeⅠinterferonopathies include Aicardi-Goutières syndrome,spondyloenchondro-dysplasia with immune dysregulation,stimulator of interferon genes-associated vasculopathy with onset in infancy,X-linked reticulate pigmentary disorder,ubiquitin-specific peptidase 18 deficiency,chronic atypical neutrophilic dermatitis with lipodystrophy,and Singleton-Merten syndrome originally.Other disorders including interferon-stimulated gene 15 deficiency and DNAseⅡdeficiency are believed to be interferonopathies as well.Intracranial calcification,skin vasculopathy,interstitial lung disease,failure to thrive,skeletal development problems and autoimmune features are common.Abnormal responses to nucleic acid stimuli and defective regulation of protein degradation are main mechanisms in disease pathogenesis.First generation Janus kinase inhibitors including baricitinib,tofacitinib and ruxolitinib are useful for disease control.Reverse transcriptase inhibitors seem to be another option for Aicardi-Goutières syndrome.Conclusions Tremendous progress has been made for the discovery of typeⅠinterferonopathies and responsible genes.Janus kinase inhibitors and other agents have potential therapeutic roles.Future basic,translational and clinical studies towards disease monitoring and powerful therapies are warranted.
