中华医学遗传学杂志最新文献

{"title":"[Clinical and genetic analysis of a case of Triadin knockout syndrome due to variant of TRDN gene and a literature review].","authors":"Huan Li, Ying Yang, Po Wang, Hongyu Xiao, Guang Yang, Yanmin Zhang, Juanli Wang","doi":"10.3760/cma.j.cn511374-20231216-00328","DOIUrl":"10.3760/cma.j.cn511374-20231216-00328","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology and clinical phenotype of a child with Triadin knockout syndrome (TKOS), and to review the relevant literature of TKOS patients due to variants of TRDN gene.</p><p><strong>Methods: </strong>A child who was admitted to the Children's Hospital of Xi'an Jiaotong University on March 19, 2023 due to sudden cardiac arrest 3 days earlier was selected as the study subject. Peripheral blood samples (2 to 3 mL) were collected from the child and her parents for the extraction of genomic DNA and whole exome sequencing (WES). Pathogenic variants were searched from databases such as the Genome Aggregation Database (gnomAD) and Online Mendelian Inheritance in Man (OMIM), and were assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Sanger sequencing was carried out for family validation of the pathogenic variants. Using keywords such as \"arrhythmias\" \"TRDN\" and \"Triadin\" both in Chinese and English, relevant literature on TKOS patients due to variants of the TRDN gene was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the time of literature retrieval was set from January 1, 2012 to December 1, 2023. This study has been approved by the Ethics Committee of the Affiliated Children's Hospital of Xi'an Jiaotong University (No. 20230097), and informed consent was obtained from the parents of the child.</p><p><strong>Results: </strong>The child had experienced syncope and cardiac arrest after exercise. Electrocardiographic examination revealed QTc interval prolongation, T-wave inversion in precordial leads V1-V3, polymorphic ventricular premature beat (VPB), and ventricular tachycardia (VT) along with increased heart rate. WES and Sanger sequencing revealed that the child has harbored a homozygous c.463del(p.E155Kfs*20) variant of the TRDN gene, for which both of the parents were heterozygous. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2+PM3). The child was ultimately diagnosed with TKOS. In total 12 publications on TOKS cases caused by TRDN gene variants were retrieved, which involved 30 patients and 28 carriers of single heterozygous variant of the TRDN gene. Among the 30 TKOS patients, 20 had carried homozygous variants of the TRDN gene, and 10 had carried compound heterozygous variants, and all had exhibited significant clinical phenotype of arrhythmia, with most cases had experienced malignant arrhythmia induced by exercise and/or excitement during infancy or early childhood, leading to recurrent syncope and cardiac arrest. Of note, none of the 28 carriers of single heterozygous variant had abnormal clinical phenotype.</p><p><strong>Conclusion: </strong>The homozygous c.463del(p.E155Kfs20) variant of the TRDN gene probably underlay the pathogenesis of cardiac arrest in this child. Above discovery has enriched the mutational spectrum of the TRDN gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1323-1329"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Analysis of EEF1A2 gene variant in a child with Global developmental delay].","authors":"Haofeng Ning, Yuqiong Chai, Wanzhen Huang, Ya'nan Wang","doi":"10.3760/cma.j.cn511374-20211001-00795","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20211001-00795","url":null,"abstract":"<p><strong>Objective: </strong>To summarize the clinical manifestations of Autosomal dominant complex neurodevelopmental disorders due to variants of EEF1A2 gene and explore their pathogenic mechanisms.</p><p><strong>Methods: </strong>A child who had visited Luoyang Maternal and Child Health Care Hospital in July 2021 for global developmental delay was selected as the study subject. Clinical data of the child was reviewed. The child was subjected to whole exome sequencing, and relevant literature was reviewed. This study has been approved by the Medical Ethics Committee of Luoyang Maternal and Child Health Care Hospital (No. YCCZ-KS-KY-2021-03).</p><p><strong>Results: </strong>The patient, a 2-year-and-4-month-old girl, had presented with global developmental delay, gait instability, low limb muscle strength, and absence language development. Her parents were both healthy and denied relevant family history. Genetic testing revealed that she has harbored a de novo heterozygous c.44A>G (p.H15R) missense variant of the EEF1A2 gene (NM_001958.5), which was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic.</p><p><strong>Conclusion: </strong>The c.44A>G (p.H15R) variant of the EEF1A2 gene probably underlay the pathogenesis in this patient. Above finding has also enriched the mutational spectrum of the EEF1A2 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1308-1315"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Research progress on epigenetic mechanism of reproductive disorders].","authors":"Nan Jiang, Xiaoli Zhao, Jiaqi Xu, Kaixi Li, Tian Xia","doi":"10.3760/cma.j.cn511374-20240524-00306","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240524-00306","url":null,"abstract":"<p><p>The \"Developmental Origins of Health and Disease, DOHaD\" theory suggests that adverse factors in early life can lead to the occurrence of chronic diseases in adulthood. In recent years, it has been discovered that maternal factors, intrauterine development environment and environmental exposure during pregnancy can mediate the changes of early egg/embryo development, promote the occurrence of reproductive disorders such as polycystic ovary syndrome, diminished ovarian reserve, and endometriosis, and induce intergenerational genetic effects. This article has reviewed the progress of research on maternal factors which may affect the pathogenesis of reproductive disorders, and expounds its mechanism from the perspectives of epigenetic mechanisms such as DNA methylation, histone modification and non-coding small RNA (miRNA) modification, with an aim to provide insights for studying the occurrence of adult reproductive disorders in early life and before pregnancy.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1393-1398"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis of a pedigree affected with Intellectual disability due to variants of two different genes].","authors":"Tingting Shi, Zengguo Ren, Ke Yang, Litao Qin, Xingxing Lei, Bing Zhang, Shixiu Liao, Li Wang","doi":"10.3760/cma.j.cn511374-20240426-00257","DOIUrl":"10.3760/cma.j.cn511374-20240426-00257","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.</p><p><strong>Methods: </strong>A Chinese pedigree which had presented at the Henan Provincial People's Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People's Hospital (Ethics No. 2019-134).</p><p><strong>Results: </strong>Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c.409+1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS1+PM2_Supporting; PVS1+PM2_Supporting+PP3).</p><p><strong>Conclusion: </strong>Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c.409+1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband's mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 11","pages":"1302-1307"},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Prenatal diagnosis of a fetus with 15q11q13 complex duplication syndrome and a literature review].","authors":"Yuxin Zhang, Jiangyang Xue, Yinwen Liu, Haibo Li","doi":"10.3760/cma.j.cn511374-20230927-00162","DOIUrl":"10.3760/cma.j.cn511374-20230927-00162","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical features and genetic etiology of a fetus with 15q11q13 complex duplication syndrome.</p><p><strong>Methods: </strong>A fetus diagnosed with 15q11q13 duplication syndrome at Ningbo Women and Children's Hospital on April 19, 2023 was selected as the study subject. Clinical data was collected, and the fetus was subjected to invasive prenatal diagnosis including G-banded karyotyping and chromosomal microarray analysis (CMA). Following the discovery of chromosomal duplication, trio-whole exome sequencing was carried out to exclude single base variants and confirm the parental original of the duplication. Optical genome mapping was also performed to delineate the structural arrangement of the duplication. Relevant literature was searched in the PubMed, Wanfang Medical Network and CNKI databases using \"15q11q13\", \"duplication\", \"hexasomy\" and \"Six fold repetition\" as the key words from January 1, 2000 to August 1, 2023 for a review of previously reported 15q11q13 hexasomy cases. This study was approved by the Ningbo Women & Children's Hospital (Ethics No. EC2020-048).</p><p><strong>Results: </strong>The fetus was found to have a mosaicism karyotype of 48,X?,+mar,+idic(15)(q13)[33]/47,X?,+idic(15)(q13)[17]. CMA and trio-WES have all shown a six-fold duplication in the PWS/AS critical region (PWACR) at 15q11.2q13.2 and quadruple duplication of 15q13.2q13.3 region, which have derived from its mother and formed supernumerary marker chromosomes (SMCs). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 15q11.2q13.2 sixfold duplication was classified as pathogenic, whilst the 15q13.2q13.3 quadruple duplication was classified as variant of uncertain significance. Literature search has identified 11 cases of 15q11q13 duplication involving hexasomy of the PWACR, with all cases showing mental retardation, language delay and hypotonia, and most of them also had motor retardation, epilepsy and mild facial dysmorphism.</p><p><strong>Conclusion: </strong>Hexasomy for the PWACR combined with tetrasomy of 15q13.2q13.3 probably underlay the left hand polydactyly, polyhydramnios and intrauterine growth retardation in this fetus.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1264-1270"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis of a child with autosomal recessive primary microcephaly due to variant of ASPM gene and a literature review].","authors":"Jie Wang, Xiaohua Wang, Lichun Zhang, Yan Huang, Rina Sha, Jin An, Yanting Wu, Zhiyuan Guo, Yueqi Jia","doi":"10.3760/cma.j.cn511374-20240123-00065","DOIUrl":"10.3760/cma.j.cn511374-20240123-00065","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).</p><p><strong>Methods: </strong>A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as \"ASPM gene\", \"microcephaly\", \"prenatal diagnosis\", \"primary microcephaly\", \"ASPM\", \"MCPH5\", \"MCPH\", \"autosomal recessive microcephaly\", and \"prenatal diagnosis on ultrasonography\" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1).</p><p><strong>Results: </strong>The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c.8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+PM2_Supporting+PP4; PVS1+PM2_Supporting+PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20).</p><p><strong>Conclusion: </strong>The compound heterozygous variants c.8044C>T (p.R2682X) and c.8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1243-1248"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical and genetic analysis of a Chinese pedigree affected with type 2 Long QT syndrome due to variant of KCNH2 gene].","authors":"Haitao Yang, Meng Sun, Jingjing Liu, Xiaosheng Chen, Xizheng Xu, Juan Hu, Lijie Yan, Jintao Wu","doi":"10.3760/cma.j.cn511374-202310100-00179","DOIUrl":"10.3760/cma.j.cn511374-202310100-00179","url":null,"abstract":"<p><strong>Objetive: </strong>To explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome (LQTS).</p><p><strong>Methods: </strong>A pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23, 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out for the proband, and candidate variant was screened through functional annotation and protein-protein interaction (PPI) analysis. Sanger sequencing was conducted to verify the pathogenicity of candidate variant. This study was approved by the Fuwai Central China Cardiovascular Hospital (Ethics No. 2019-15).</p><p><strong>Results: </strong>WES revealed that the proband has harbored a missense variant of the KCNH2 gene, namely c.1478A>G (p.Tyr493Cys), which was confirmed by Sanger sequencing to have inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_supporting+PM5+PP3+PP4).</p><p><strong>Conclusion: </strong>The KCNH2 gene c.1478A>G (p.Tyr493Cys) variant probably underlay the type 2 LQTS in this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1218-1224"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical features and genetic analysis of two Chinese pedigrees affected with Lymphedema-Distichiasis syndrome].","authors":"Jing Li, Limin Yuan, Shanshan Zhai, Naiqi Li, Handuo Wang, Xiao Han, Lanlan Zhao, Juan Li, Shihong Cui, Ling Liu","doi":"10.3760/cma.j.cn511374-20240807-00426","DOIUrl":"10.3760/cma.j.cn511374-20240807-00426","url":null,"abstract":"<p><strong>Objective: </strong>To explore the prenatal and postnatal features and genetic characteristics of patients with Lymphedema-Distichiasis syndrome (LDS) due to variants of FOXC2 gene.</p><p><strong>Methods: </strong>A retrospective analysis was carried out on the phenotypic information, fetal ultrasound image, and genetic testing of two Chinese pedigrees diagnosed at the Third Affiliated Hospital of Zhengzhou University. A literature review was also carried out by searching the China National Knowledge Infrastructure (CNKI), Wanfang Database, and PubMed databases dated from January 2010 to June 2024 using keywords \"Lymphedema-Distichiasis syndrome \" and \"FOXC2 \". This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-046-01).</p><p><strong>Results: </strong>Neither family was found to harbor chromosomal aneuploidy or pathogenic CNVs larger than 100 kb. The fetuses from pedigree 1 and pedigree 2 were respectively found to be heterozygous for a c.361C>T (p.R121C) variant and a c.168C>A (p.Y56*) variant of the FOXC2 gene. Both variants were paternally derived. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as pathogenic and likely pathogenic, respectively. Literature search has identified 20 articles, and combined with our cases, a total of 117 patients were identified. Among them, 13 had shown prenatal phenotypes, primarily with increased nuchal translucency (NT) (12/13), urinary abnormalities (5/12), and fetal edema (4/13). Postnatal phenotypes were observed in 110 cases, mainly as distichiasis (87/110) and lymphedema (73/110). Only 6 cases had both prenatal and postnatal phenotypes. A total of 32 genetic variants were identified.</p><p><strong>Conclusion: </strong>The primary prenatal manifestations of LDS include increased NT, fetal edema, pleural and abdominal effusion, and separation of renal collecting system. Postnatal phenotypes are primarily characterized by lymphedema, distichiasis, and spinal extradural arachnoid cysts. Discovery of the c.168C>A variant has expanded the spectrum of FOXC2 gene mutations in China.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1441-1447"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Genetic analysis of a child with 18q terminal deletion and aortic regurgitation and a literature review].","authors":"Huimin Cui, Fang Zhang, Ting Yin, Zhiwei Wang, Xin Wang, Qingqing Gu, Jinglu Zhang, Juan Tan","doi":"10.3760/cma.j.cn511374-20231122-00270","DOIUrl":"10.3760/cma.j.cn511374-20231122-00270","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic characteristics of a child with 18q terminal deletion syndrome.</p><p><strong>Methods: </strong>Clinical data of a child presented at the Lianyungang Maternal and Child Health Care Hospital on July 20, 2023 was collected. Peripheral blood sample from the child was subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). Relevant literature was searched from CNKI, WanFang and PubMed databases over the past decade (from November 1, 2013 to November 1, 2023) using keywords including \"18q-syndrome\", \"18q deletion syndrome\" and \"18q terminal deletion\". This study was approved by the Lianyungang Maternal and Child Health Care Hospital (Ethics No. LYG-MER2021017).</p><p><strong>Results: </strong>The child, a 4-year-and-6-month-old female, had manifested short stature, intellectual disability, distinctive facial features, aortic regurgitation, auditory canal atresia, and white matter lesions. She was found to have a karyotype of 46,XX,del(18)(q21), whilst the result of CMA was arr[GRCh37]18q21.33q23(60065821_77317445)×1. Both of her parents were found to have a normal karyotype. Literature review has retrieved 7 reports which involved 11 cases with a terminal 18q23 deletion. The phenotypes of cardiac abnormalities have been diverse, with pulmonary stenosis, atrial septal defect and ventricular septal defect being most common.</p><p><strong>Conclusion: </strong>The 18q terminal deletion probably underlay the multiple congenital anomalies and mental retardation in this child.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1259-1263"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical and genetic analysis of a Chinese pedigree affected with Familial focal epilepsy with variable foci due to variant of NPRL3 gene].","authors":"Yongli Li, Yifan Yang, Jigang Qiu, Liangliang Lu","doi":"10.3760/cma.j.cn511374-20231108-00235","DOIUrl":"10.3760/cma.j.cn511374-20231108-00235","url":null,"abstract":"<p><strong>Objetive: </strong>To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).</p><p><strong>Methods: </strong>A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).</p><p><strong>Results: </strong>WES revealed that the proband has harbored a heterozygous c.1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband's father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3).</p><p><strong>Conclusion: </strong>The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1213-1217"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}