Background: The high consanguinity in Middle East increases the risk of genetic diseases, including primary immunodeficiency diseases (PID). Objectives: This study was aimed at determining the rate of positive family ...Background: The high consanguinity in Middle East increases the risk of genetic diseases, including primary immunodeficiency diseases (PID). Objectives: This study was aimed at determining the rate of positive family history of PID, the overall rate and type of consanguinity, and their effects on delay age during diagnosis of PID. Materials and methods: A retrospective analysis was conducted on 131 children with PID (aged 0 - 14 years) managed at Hamad General Hospital during 1998-2012. Results: Data on 131 patients (75 males & 56 females) of 82 families was analyzed. The most common phenotype of PID was predominantly antibody deficiency (23.7%). The onset age was 24.01 months and delay age 18.7 months. Family history of PID was 66.4% (38.7% in predominantly antibody deficiency and 100% in diseases of immune dysregulation). Positive family history significantly (p = 0.004) reduced the delay age of PID diagnosis by 52.9%. The consanguinity rate was 61.1% (32.3% in the predominantly antibody ID to 96% in the phagocyte defects group), where paternal cousin ranked the highest type (57.5%). Conclusions: This study indicates that family history is common in children with PID and helpful in reducing the delay age. Consanguinity among families of affected children is also high (higher than healthy population). Paternal parallel cousin marriages are the most common type of consanguinity. For a practicing physician, family history is a simple and useful tool when suspecting PID in children. Primary prevention of PID in Middle East communities should consider consanguinity reduction through public awareness and education and premarital counseling programs.展开更多
This study was investigated whether parental consanguinity in males has an effect on or relationship with some infertile subgroups and some semen and hormone parameters. The charts of 2651 infertile males were evaluat...This study was investigated whether parental consanguinity in males has an effect on or relationship with some infertile subgroups and some semen and hormone parameters. The charts of 2651 infertile males were evaluated retrospectively for parental consanguinity ratios, sperm counts, motility parameters and hormonal values from the records of 2651 infertile males. In 1260 eligible males the first cousin parental consanguinity ratio was 22.6%. In 119 males with nonobstructive azoospermic (NOA) and 430 males with normal sperm counts, the ratios were 34.5% and 20.9%, respectively (p = 0.002). In the NOA group the parental consanguinity ratios were 27.1% (23/85) and 52.9% (18/34) in males with FSH values of >7.6 and 7.6 mIU/ml, respectively (p = 0.007). In males with normal sperm counts if the parents were first cousins, both sperm counts and motility parameters were significantly reduced when compared with the others. To our knowledge, this is the first study of consanguinity ratios among some infertile subgroups. In males with parental consanguinity lower sperm counts and motility ratios in normozoospermic males and lower FSH levels in the NOA group might show a relation with some genetically transmitted defects.展开更多
BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the gene...BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.展开更多
AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi...AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.展开更多
BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical...BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.展开更多
AIM:To study frequency of blood groups,prevalence of sickle-cell anemia trait and glucose-6-phosphate dehydrogenase deficiency(G6PD),among consanguineous Yansi tribe.METHODS:A total of 525 blood samples were collected...AIM:To study frequency of blood groups,prevalence of sickle-cell anemia trait and glucose-6-phosphate dehydrogenase deficiency(G6PD),among consanguineous Yansi tribe.METHODS:A total of 525 blood samples were collected,of which 256 among the Yansi population,and269 for the unrelated control group in the Bandunduprovince of Democratic Republic of Congo.Blood group antigens were determined in the following systems:ABO,Rh,Kell,Duffy,Kidd and MNS.Blood grouping and extended phenotype tests were performed according to standard immunohematological procedures.Spot tests and tandem mass spectrometry were used respectively for the assessment of G6PD and sickle-cell anemia trait.RESULTS:The frequency of ABO phenotypes conformed to the following order O>A>B>AB with notably 62.5%,23.8%,12.1%and 1.6%for the Yansi,and 54.6%,27.5%,14.1%and 3.7%for the unrelated control group,respectively(P=0.19).As for the Rh phenotypes,the most frequent were cc D.ee,cc D.Ee,Cc D.ee,corresponding to 71.5%,12.1%and 12.1%for the Yansi,and 70.6%,15.6%and 8.2%,for the unrelated control group(P=0.27).The frequency of MN and Ss phenotypes were statistically different between groups(P=0.0021 and P=0.0006).G6PD was observed in 11.3%of subjects in the Yansi group,and in 12.4%of controls(P=0.74).The sickle-cell anemia trait was present in 22.4%of Yansi subjects and 17.8%in the control group(P=0.24).Miscarriages and deaths in young age were more common among Yansi people.CONCLUSION:This study shows a significant difference in MNS blood group distribution between the Yansi tribe and a control population.The distribution of other blood groups and the prevalence of hemoglobinopathies did not differ in the Yansi tribe.展开更多
<strong>Introduction: </strong><span style="font-family:;" "=""><span style="font-family:Verdana;">The objective of this study was to evaluate the epidemiolog...<strong>Introduction: </strong><span style="font-family:;" "=""><span style="font-family:Verdana;">The objective of this study was to evaluate the epidemiological, diagnostic and therapeutic aspects of cardiogenic shock in children at the Albert Royer Children’s Hospital in Dakar. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">This was a retrospective, descriptive and analytical study from January 2020 to February 2021, including all children aged 2 months to 16 years hospitalised for cardiogenic shock diagnosed on the basis of clinical and ultrasound criteria. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">During the study, 38 patients were hospitalised for cardiogenic shock. The hospital prevalence was 4.2%. The mean age of onset of shock was 64 months, and there was a predominance of females with a sex ratio of 1.92. Consanguinity was found in 42% of the patients. Consanguinity was found in 42% of patients. Infection was identified as a trigger for cardiogenic shock in 18 (52.9%) of our patients. The most common type of heart disease was rheumatic heart disease in 12 (32%) of the patients. The mortality rate was 65.8%. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">Cardiogenic shock is a diagnostic and therapeutic emergency. Its prevalence and mortality are still high in developing countries.</span></span>展开更多
BACKGROUND Lysinuric protein intolerance(LPI)is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene.The metabolic imbalance in absorption and excretion of dibasic amino acids is consi...BACKGROUND Lysinuric protein intolerance(LPI)is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene.The metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of LPI.The disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment,respiratory involvement,renal failure and autoimmune complications.AIM To determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani children.METHODS The study was conducted at the Biochemical Genetic Lab,Department of Pathology and Laboratory Medicine,AKU Plasma,and urine amino acid quantification data from January 2013 to October 2018 was included in this study.The amino acids were analyzed by high performance liquid chromatography.Prestructured requisition forms were used to obtain the clinicopathological data.Statistical analysis was done by Microsoft Excel 2017.RESULTS A total of 6 patients were recognized.All the patients were male(100%).The mean age was 24 mo±10 d.All the patients had low plasma concentration of lysine,ornithine and arginine,whereas increased levels of lysine,ornithine and arginine in urine were observed in 2 patients.History of consanguineous marriage was present in all patients(100%).The most observed clinical symptom was feeding difficulty followed by failure to thrive(83.3%)and developmental delay(66.6%).Hepatomegaly was present in all patients(100%).No mutation analysis was done.CONCLUSION This study portrays the biochemical and clinical spectrum of LPI in Pakistan.Although clinical manifestations appeared in the first 2 years of life,most of them suffered a delay in undergoing diagnostic workup.展开更多
Dear Editor,I have carefully read the article entitled 'Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene',published by Shakil et al^([1])in 201...Dear Editor,I have carefully read the article entitled 'Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene',published by Shakil et al^([1])in 2016 and found it very interesting展开更多
Amelogenesis imperfecta is an unusual hereditory disorder affecting both primary and permanent dentition. We present a rare case of hypocalcified auto-somal recessive amelogenesis imperfecta occuring in primary dentit...Amelogenesis imperfecta is an unusual hereditory disorder affecting both primary and permanent dentition. We present a rare case of hypocalcified auto-somal recessive amelogenesis imperfecta occuring in primary dentition in a 7-year-old girl with a family history of consanguineous marriage. Clinical and radiological examination revealed discoloration and hypoplasia of enamel with easy chipping affecting both maxillary and mandibular dentition.展开更多
A first cousin marriage couple and their 8-year-old identical twin daughters with concomitant strabismus are described.This family would indicate an autosomal recessive inheritance in concomitant strabismus.
Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resul...Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.展开更多
As an important witness to the rural industry in the agricultural era,traditional handicraft villages have attracted renewed attention in the contemporary context of intangible cultural heritage protection.The dual ch...As an important witness to the rural industry in the agricultural era,traditional handicraft villages have attracted renewed attention in the contemporary context of intangible cultural heritage protection.The dual characteristics of their traditional cultural heritage and modern economic benefits make these villages an important carrier of the dynamic inheritance and development of the heritages under the background of rural revitalization.This paper takes a stonemason village of Xizhuang in Xinjiang County,Shanxi Province,as an example,and reveals the evolutionary characteristics of traditional handicraft villages in the process of transition from agricultural to industrial society from the“social-spatial”perspective.In the agricultural era,the kinship,production organization,and religious beliefs of traditional handicraft villages were closely linked under the blood relationship in a clan-based structure,forming a“social-spatial”trinity composed of“residence,production,and spirit.”In the industrial era,the development of handicraft economy results in the transformation of the“social-spatial”form of the settlement,the social structure shrank from clan control to nuclear family domination,the production space began to be stripped away from villages,the living space changed from gathered clan living to separated-family homes,and the spiritual place was transformed into public space.However,due to the inter-generational transmission of handicrafts based on blood relationship,the consanguinity community has always been the main carrier for the continuity of skills,and has become the stable foundation for maintaining the“social-spatial”form of the village.Therefore,the adaptive transition of traditional handicraft villages in the context of socio-economic transformation continues the interconnection among society,economy,and space,and presents a unique vitality and comparative stability.展开更多
文摘Background: The high consanguinity in Middle East increases the risk of genetic diseases, including primary immunodeficiency diseases (PID). Objectives: This study was aimed at determining the rate of positive family history of PID, the overall rate and type of consanguinity, and their effects on delay age during diagnosis of PID. Materials and methods: A retrospective analysis was conducted on 131 children with PID (aged 0 - 14 years) managed at Hamad General Hospital during 1998-2012. Results: Data on 131 patients (75 males & 56 females) of 82 families was analyzed. The most common phenotype of PID was predominantly antibody deficiency (23.7%). The onset age was 24.01 months and delay age 18.7 months. Family history of PID was 66.4% (38.7% in predominantly antibody deficiency and 100% in diseases of immune dysregulation). Positive family history significantly (p = 0.004) reduced the delay age of PID diagnosis by 52.9%. The consanguinity rate was 61.1% (32.3% in the predominantly antibody ID to 96% in the phagocyte defects group), where paternal cousin ranked the highest type (57.5%). Conclusions: This study indicates that family history is common in children with PID and helpful in reducing the delay age. Consanguinity among families of affected children is also high (higher than healthy population). Paternal parallel cousin marriages are the most common type of consanguinity. For a practicing physician, family history is a simple and useful tool when suspecting PID in children. Primary prevention of PID in Middle East communities should consider consanguinity reduction through public awareness and education and premarital counseling programs.
文摘This study was investigated whether parental consanguinity in males has an effect on or relationship with some infertile subgroups and some semen and hormone parameters. The charts of 2651 infertile males were evaluated retrospectively for parental consanguinity ratios, sperm counts, motility parameters and hormonal values from the records of 2651 infertile males. In 1260 eligible males the first cousin parental consanguinity ratio was 22.6%. In 119 males with nonobstructive azoospermic (NOA) and 430 males with normal sperm counts, the ratios were 34.5% and 20.9%, respectively (p = 0.002). In the NOA group the parental consanguinity ratios were 27.1% (23/85) and 52.9% (18/34) in males with FSH values of >7.6 and 7.6 mIU/ml, respectively (p = 0.007). In males with normal sperm counts if the parents were first cousins, both sperm counts and motility parameters were significantly reduced when compared with the others. To our knowledge, this is the first study of consanguinity ratios among some infertile subgroups. In males with parental consanguinity lower sperm counts and motility ratios in normozoospermic males and lower FSH levels in the NOA group might show a relation with some genetically transmitted defects.
文摘BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.
基金Supported by Qatar Diabetic Association and Qatar National Research Fund, QNRF UREP 07-099-3-023
文摘AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.
文摘BACKGROUND Risk factors such as hereditary, ecological, and metabolic are interrelated and contribute to the development of type 2 diabetes mellitus. Family history(FH) of diabetes mellitus, age, obesity, and physical inactivity are some of the risk factors for the development of type 2 diabetes.AIM To study various aetiological determinants and risk factors for type 2 diabetes in Bangalore, India. This retrospective study examined questionnaire from patients attending the Diabetes Clinic.METHODS Data on various parameters were obtained through a questionnaire from 533 patients on the first visit to the diabetes clinic. Data regarding various aetiological determinants and risk factors viz.: Genetic risk factor and few modifiable risk factors were collected. Chi-squared test was used for statistical analysis.RESULTS A higher incidence of type 2 diabetes in males and younger population was observed in Bangalore, India. Obesity and FH were significant risk factors for not only type 2 diabetes but also early onset of diabetes. In addition, maternal history of type 2 diabetes and consanguinity increased incidence of early onset type 2 diabetes.CONCLUSION Risk factors such as obesity and FH(maternal history of type 2 diabetes) and consanguinity may play an important role in screening of family members of type 2 diabetes patients which may lead to early intervention and reduced risk of subsequent complications. Moreover, susceptible population can be counselled for the management of the type 2 diabetes including periodic investigation of blood glucose levels and lifestyle changes.
文摘AIM:To study frequency of blood groups,prevalence of sickle-cell anemia trait and glucose-6-phosphate dehydrogenase deficiency(G6PD),among consanguineous Yansi tribe.METHODS:A total of 525 blood samples were collected,of which 256 among the Yansi population,and269 for the unrelated control group in the Bandunduprovince of Democratic Republic of Congo.Blood group antigens were determined in the following systems:ABO,Rh,Kell,Duffy,Kidd and MNS.Blood grouping and extended phenotype tests were performed according to standard immunohematological procedures.Spot tests and tandem mass spectrometry were used respectively for the assessment of G6PD and sickle-cell anemia trait.RESULTS:The frequency of ABO phenotypes conformed to the following order O>A>B>AB with notably 62.5%,23.8%,12.1%and 1.6%for the Yansi,and 54.6%,27.5%,14.1%and 3.7%for the unrelated control group,respectively(P=0.19).As for the Rh phenotypes,the most frequent were cc D.ee,cc D.Ee,Cc D.ee,corresponding to 71.5%,12.1%and 12.1%for the Yansi,and 70.6%,15.6%and 8.2%,for the unrelated control group(P=0.27).The frequency of MN and Ss phenotypes were statistically different between groups(P=0.0021 and P=0.0006).G6PD was observed in 11.3%of subjects in the Yansi group,and in 12.4%of controls(P=0.74).The sickle-cell anemia trait was present in 22.4%of Yansi subjects and 17.8%in the control group(P=0.24).Miscarriages and deaths in young age were more common among Yansi people.CONCLUSION:This study shows a significant difference in MNS blood group distribution between the Yansi tribe and a control population.The distribution of other blood groups and the prevalence of hemoglobinopathies did not differ in the Yansi tribe.
文摘<strong>Introduction: </strong><span style="font-family:;" "=""><span style="font-family:Verdana;">The objective of this study was to evaluate the epidemiological, diagnostic and therapeutic aspects of cardiogenic shock in children at the Albert Royer Children’s Hospital in Dakar. </span><b><span style="font-family:Verdana;">Methods: </span></b><span style="font-family:Verdana;">This was a retrospective, descriptive and analytical study from January 2020 to February 2021, including all children aged 2 months to 16 years hospitalised for cardiogenic shock diagnosed on the basis of clinical and ultrasound criteria. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">During the study, 38 patients were hospitalised for cardiogenic shock. The hospital prevalence was 4.2%. The mean age of onset of shock was 64 months, and there was a predominance of females with a sex ratio of 1.92. Consanguinity was found in 42% of the patients. Consanguinity was found in 42% of patients. Infection was identified as a trigger for cardiogenic shock in 18 (52.9%) of our patients. The most common type of heart disease was rheumatic heart disease in 12 (32%) of the patients. The mortality rate was 65.8%. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">Cardiogenic shock is a diagnostic and therapeutic emergency. Its prevalence and mortality are still high in developing countries.</span></span>
文摘BACKGROUND Lysinuric protein intolerance(LPI)is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene.The metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of LPI.The disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment,respiratory involvement,renal failure and autoimmune complications.AIM To determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani children.METHODS The study was conducted at the Biochemical Genetic Lab,Department of Pathology and Laboratory Medicine,AKU Plasma,and urine amino acid quantification data from January 2013 to October 2018 was included in this study.The amino acids were analyzed by high performance liquid chromatography.Prestructured requisition forms were used to obtain the clinicopathological data.Statistical analysis was done by Microsoft Excel 2017.RESULTS A total of 6 patients were recognized.All the patients were male(100%).The mean age was 24 mo±10 d.All the patients had low plasma concentration of lysine,ornithine and arginine,whereas increased levels of lysine,ornithine and arginine in urine were observed in 2 patients.History of consanguineous marriage was present in all patients(100%).The most observed clinical symptom was feeding difficulty followed by failure to thrive(83.3%)and developmental delay(66.6%).Hepatomegaly was present in all patients(100%).No mutation analysis was done.CONCLUSION This study portrays the biochemical and clinical spectrum of LPI in Pakistan.Although clinical manifestations appeared in the first 2 years of life,most of them suffered a delay in undergoing diagnostic workup.
文摘Dear Editor,I have carefully read the article entitled 'Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene',published by Shakil et al^([1])in 2016 and found it very interesting
文摘Amelogenesis imperfecta is an unusual hereditory disorder affecting both primary and permanent dentition. We present a rare case of hypocalcified auto-somal recessive amelogenesis imperfecta occuring in primary dentition in a 7-year-old girl with a family history of consanguineous marriage. Clinical and radiological examination revealed discoloration and hypoplasia of enamel with easy chipping affecting both maxillary and mandibular dentition.
文摘A first cousin marriage couple and their 8-year-old identical twin daughters with concomitant strabismus are described.This family would indicate an autosomal recessive inheritance in concomitant strabismus.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.82001221 and 81788101)the National Key Research and Development Program of China(Nos.2022YFC2703900 and 2022YFC2703903)the CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-018,2022-I2M-JB-004 and 2017-I2M-B&R-05).
文摘Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine.Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation.Here,a Pakistani family with parental consanguinity was presented,characterized with severe intellectual disability(ID),spastic paraplegia,and deafness.Homozygosity mapping,integrated single nucleotide polymorphism(SNP)array,whole-exome sequencing,and whole-genome sequencing were performed,and homozygous variants in TMEM141(c.270G>A,p.Trp90^(*)),DDHD2(c.411+767_c.1249-327del),and LHFPL5(c.250delC,p.Leu84^(*))were identified.A Tmem141^(p.Trp90^(*)/p.Trp90^(*))mouse model was generated.Behavioral studies showed impairments in learning ability and motor coordination.Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells.Transmission electron microscopy showed abnormal mitochondrial morphology.Furthermore,studies on a human in vitro neuronal model(SH-SY5Y cells)with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function,possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model.Conclusively,panoramic variation analysis revealed that multilocus genomic variations of TMEM141,DDHD2,and LHFPL5 together caused variable phenotypes in patient.Notably,the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.
基金a part of the Research on the Spatial Form and Protection of Traditional Villages in Ningshao Area Based on the Theory of“Society-Space”that is supported by the National Natural Sciences Fund(No.52078228)。
文摘As an important witness to the rural industry in the agricultural era,traditional handicraft villages have attracted renewed attention in the contemporary context of intangible cultural heritage protection.The dual characteristics of their traditional cultural heritage and modern economic benefits make these villages an important carrier of the dynamic inheritance and development of the heritages under the background of rural revitalization.This paper takes a stonemason village of Xizhuang in Xinjiang County,Shanxi Province,as an example,and reveals the evolutionary characteristics of traditional handicraft villages in the process of transition from agricultural to industrial society from the“social-spatial”perspective.In the agricultural era,the kinship,production organization,and religious beliefs of traditional handicraft villages were closely linked under the blood relationship in a clan-based structure,forming a“social-spatial”trinity composed of“residence,production,and spirit.”In the industrial era,the development of handicraft economy results in the transformation of the“social-spatial”form of the settlement,the social structure shrank from clan control to nuclear family domination,the production space began to be stripped away from villages,the living space changed from gathered clan living to separated-family homes,and the spiritual place was transformed into public space.However,due to the inter-generational transmission of handicrafts based on blood relationship,the consanguinity community has always been the main carrier for the continuity of skills,and has become the stable foundation for maintaining the“social-spatial”form of the village.Therefore,the adaptive transition of traditional handicraft villages in the context of socio-economic transformation continues the interconnection among society,economy,and space,and presents a unique vitality and comparative stability.
