中华医学遗传学杂志最新文献

{"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}

{"title":"[Clinical and genetic analysis of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy].","authors":"Liuyu Sun, Huijie Xiao, Yali Ren, Ke Xu, Xuhui Zhong, Hongwen Zhang, Yuegui Zeng, Fang Wang","doi":"10.3760/cma.j.cn511374-20240305-00144","DOIUrl":"10.3760/cma.j.cn511374-20240305-00144","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy.</p><p><strong>Methods: </strong>A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by the Peking University First Hospital (Ethics No. 2016[1029]).</p><p><strong>Results: </strong>The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c.737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+PM2_Supporting+PM3+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b.</p><p><strong>Conclusion: </strong>The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1231-1237"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355967","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 ACADVL gene variant in a Chinese pedigree affected with Very-long-chain acl-CoA dehydrogenase deficiency].","authors":"Haofeng Ning, Yuqiong Chai, Jieqiong Wang, Ya'nan Wang","doi":"10.3760/cma.j.cn511374-20210525-00441","DOIUrl":"10.3760/cma.j.cn511374-20210525-00441","url":null,"abstract":"<p><strong>Objective: </strong>To carry out genetic testing on a child diagnosed with Very-long-chain acyl-CoA dehydrogenase deficiency (VLADD) in order to provide a basis for genetic counseling and prenatal diagnosis for his family.</p><p><strong>Methods: </strong>Whole exome sequencing was performed for the proband. Candidate variant sites in the ACADVL gene were verified by Sanger sequencing, and their pathogenicity was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was performed on the fetus upon subsequent pregnancy. This study was approved by the Luoyang Maternal and Child Health Care Hospital (Ethics No. ).</p><p><strong>Results: </strong>The proband was found to harbor compound heterozygous variants of the ACADVL gene, namely c.1532G>A and 1827+2_1827+12del, which were inherited from his mother and father, and classified as likely pathogenic and pathogenic, respectively. By combining the clinical manifestations of the proband and the results of blood tandem mass spectrometry and genetic testing, the child was ultimately diagnosed as cardiomyopathy type VLADD. Prenatal diagnosis showed that the fetus has carried the same compound heterozygous variants, and the couple had opted to terminate the pregnancy.</p><p><strong>Conclusion: </strong>The c.1532G>A/1827+2_1827+12del compound heterozygous variants of the ACADVL gene probably underlay the pathogenesis of VLADD in this pedigree. The discovery of the 1827+2_1827+12del variant has enriched the mutational spectrum of the ACADVL gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1225-1230"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355964","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 child with Spondyloocular syndrome due to compound heterozygous variants of XYLT2 gene].","authors":"Miaomiao Chen, Shengxiang Huang, Yu Tian, Xinghan Wu, Yu Zheng, Shuju Zhang, Yu Peng, Hua Wang","doi":"10.3760/cma.j.cn511374-20240307-00155","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240307-00155","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease.</p><p><strong>Methods: </strong>A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children's Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. KYAQ2022-263).</p><p><strong>Results: </strong>The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c.1103_1104delAG (p.Gln368Argfs*8) and c.1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c.1103_1104delAG was predicted as a pathogenic variant (PVS1+PM2_Supporting+PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+PM3+PM2_Supporting+PP4).</p><p><strong>Conclusion: </strong>The c.1103_1104delAG and c.1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1316-1322"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630139","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 characteristics and genetic analysis of a child with Cantú syndrome due to variant of ABCC9 gene].","authors":"Mengjun Xiao, Fangjie Wang, Yingying Li, Xiaoli Yao, Weina Hou, Kun He","doi":"10.3760/cma.j.cn511374-20230616-00366","DOIUrl":"10.3760/cma.j.cn511374-20230616-00366","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and pathogenic variant in a child with Cantú syndrome (CS).</p><p><strong>Methods: </strong>A male who was admitted to the Children's Hospital Affiliated to Zhengzhou University on February 23, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole-exome sequencing (WES). Candidate variant was verified by Sanger sequencing. This study was approved by the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2023-K-087).</p><p><strong>Results: </strong>The child, a 3-year-and-2-month-old male, was born with hirsutism, with heavy hair all over the body and peculiar facial features. Routine echocardiography 1 month before had discovered atrial septal defect. Sequencing revealed that the child has harbored a heterozygous c.2438G>C (p.S813T) variant of the ABCC9 gene, which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2438G>C variant was classified as likely pathogenic (PS2+PM2_Supporting+PP3).</p><p><strong>Conclusion: </strong>The heterozygous c.2438G>C variant of the ABCC9 gene probably underlay the pathogenesis of CS in this child.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1249-1254"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355911","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 fetus with Coffin-Siris syndrome 2 due to a novel variant of ARID1A gene].","authors":"Yuqiong Chai, Jieqiong Wang, Yaxin Wang, Pai Zhang, Jiapei Jin, Ya'nan Wang","doi":"10.3760/cma.j.cn511374-20231214-00322","DOIUrl":"10.3760/cma.j.cn511374-20231214-00322","url":null,"abstract":"<p><strong>Objective: </strong>To explore the genetic etiology of a fetus with Coffin-Siris syndrome (CSS).</p><p><strong>Methods: </strong>A fetus with abnormal ultrasound findings detected at Luoyang Maternal and Child Health Care Hospital in July 2023 was selected as the study subject. Clinical data were analyzed retrospectively. Whole exome sequencing was carried out on fetal tissue and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Luoyang Maternal and Child Health Care Hospital (Ethics No. LYFY-YCCZ-2023011).</p><p><strong>Results: </strong>Color Doppler ultrasound at 16⁺ gestational weeks revealed bilateral ventriculomegaly and cerebellar hypoplasia in the fetus. Trio-WES found that the fetus has harbored a heterozygous c.553C>T (p.Gln185Ter) variant of the ARID1A gene, which was verified by Sanger sequencing to have a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.553C>T (p.Gln185Ter) variant of the ARID1A gene was classified as pathogenic (PVS1+PS2_Supporting+PM2_Supporting).</p><p><strong>Conclusion: </strong>The fetus was diagnosed with CSS type 2, and the heterozygous c.553C>T (p.Gln185Ter) variant of the ARID1A gene probably underlay its brain malformations.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1255-1258"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355946","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 and prenatal diagnosis of a Chinese pedigree affected with Complete androgen insensitivity syndrome due to a novel variant of AR gene].","authors":"Fanrong Meng, Xiaozhou Li, Yunfang Shi, Duan Ju, Xiuyan Wang, Chunying Wang, Xuebing Li, Wenjun Yu, Yingmei Wang, Xuexia Zhou","doi":"10.3760/cma.j.cn511374-20231014-00191","DOIUrl":"10.3760/cma.j.cn511374-20231014-00191","url":null,"abstract":"<p><strong>Objetive: </strong>To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).</p><p><strong>Methods: </strong>A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome (SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070).</p><p><strong>Results: </strong>The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46,XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c.1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister's first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PM4+PP3_Moderate+PP4).</p><p><strong>Conclusion: </strong>The c.1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians' thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"41 10","pages":"1206-1212"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355916","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}