中华医学遗传学杂志最新文献

{"title":"[Analysis of a child with X-linked intellectual disability type 100 due to variant of KIF4A gene and a literature review].","authors":"Xiaoxuan Fan, Zhengfang Chen, Xiaoyan Xuan, Xiaoke Zhao","doi":"10.3760/cma.j.cn511374-20241028-00565","DOIUrl":"10.3760/cma.j.cn511374-20241028-00565","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES).</p><p><strong>Methods: </strong>A child presented at the Children's Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1).</p><p><strong>Results: </strong>The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China.</p><p><strong>Conclusion: </strong>The c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 10","pages":"307-313"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081176","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 analysis of a child with heterotopic ventricular gray matter Renpenning syndrome caused by PQBP1 gene mutation and a literature review].","authors":"Yazhen Fan, Jianchuang Zhao, Qian Chen, Xianjie Huang, Fan Li, Junying Qiao","doi":"10.3760/cma.j.cn511374-20240923-00502","DOIUrl":"10.3760/cma.j.cn511374-20240923-00502","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To explore the genetic etiology of a child with Renpenning syndrome (RS), and review the literature on the clinical characteristics and gene mutations of RS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A child with RS (patient 1) who was diagnosed and treated in the Pediatric Intensive Care Unit of the Third Affiliated Hospital of Zhengzhou University in November 2023 was selected as the research object. The medical history, family history, physical examination, cerebrospinal fluid examination, echocardiography, brain magnetic resonance imaging (MRI), brain magnetic resonance angiography, cardiac coronary CT angiography and intelligence quotient (IQ) score of child 1 were retrospectively collected. Peripheral venous blood samples were collected from patient 1, his parents, sister and brother, respectively. Genomic DNA was extracted from the child and his family members, and Trios-whole exome sequencing (Trios-WES) was performed. Sanger sequencing was used to verify the pedigree. Bioinformatics softwares (Mutation Taster, REVEL, SIFT, PolyPhen-2, GERP++, SWISS-MODEL) were applied. The pathogenicity of the detected variants was rated according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Classification of Genetic Variants (hereinafter referred to as the ACMG Guidelines). \"PQBP1 gene\" \"Renpenning syndrome\" \"PQBP1 gene\" \"Renpenning syndrome\" were used as keywords in Chinese and English, respectively. Case reports of patients with RS caused by PQBP1 gene variants were retrieved from Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed database. The clinical features and gene variants of RS caused by PQBP1 gene variants were summarized and analyzed. This study was reviewed by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Approval No. 2024-334-01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The patient 1, a 12-year-old boy, was admitted to the hospital due to fever and disturbance of consciousness. Cerebrospinal fluid test showed viral encephalitis caused by human herpesvirus 7 infection. The main clinical manifestations were unusual facies (microcephaly, long narrow face, microphthalmos, superior oblique palpebral fissure, hypertelorism of inner canthus, bulbous nasal columella) and mental retardation. Auxiliary examination showed than patient 1 had atrial septal defect, nodular heterotopia in the posterior horn of the left ventricle, angiodysplasia, and low IQ. The disease began in infancy, and there was no family history of related diseases. A hemizygous deletion, c.459_462del (p.Arg153SerfsTer41), was identified in exon 5 of the PQBP1 gene in patient 1, which was inherited from his mother by Sanger sequencing. The results of bioinformatics analysis showed that the mutation was harmful. This variant was rated as pathogenic (PVS1+PS4+PM2_Supporting+PP3) according to ACMG Guidelines. According to the literature sea","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"314-321"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081181","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":"[Molecular cytogenetic analysis and diagnosis of three fetuses with psu idic(Y)(q11.22) using a combination of multiple techniques].","authors":"Xuejiao Chen, Meizhen Dai, Milei Zhu, Weiwu Shi","doi":"10.3760/cma.j.cn511374-20241112-00585","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241112-00585","url":null,"abstract":"<p><strong>Objective: </strong>To explore the molecular cytogenetic characteristics of three fetuses with psu idic(Y)(q11.22) using a combination of multiple methods.</p><p><strong>Methods: </strong>A total of 11 000 pregnant women who underwent prenatal diagnosis at the Prenatal Diagnosis Center of Taizhou City from January 2019 to October 2024 were selected as the study subjects. Chromosome karyotype analysis (G-banding) and copy number variation analysis based on next-generation sequencing (NGS) were performed on the amniotic fluid/cord blood samples of the 11 000 fetuses. For cases suspected of Y chromosome abnormalities, C-banding and/or fluorescence in situ hybridization (FISH) and AZF microdeletion testing were additionally conducted. This study has been reviewed and approved by the Medical Ethics Committee of Taizhou Hospital, Zhejiang Province (Ethics No. KL20240860).</p><p><strong>Results: </strong>Among the 11,000 prenatal samples undergoing concurrent karyotype and copy number variation analysis, two fetuses with 45,X/46,X,psu idic(Y)(q11.22) mosaicism and one fetus with 46,X,psu idic(Y)(q11.22) were detected. FISH detection indicated that approximately 66.7% of the cells in fetus 2 exhibited a dicentric Y chromosome, and the metaphase karyotype supported the presence of a pseudodicentric chromosome. AZF testing revealed complete deletion of the AZFb+AZFc regions in fetus 2 and fetus 3.</p><p><strong>Conclusion: </strong>Conventional G-banding karyotype analysis for psu idic(Y)(q11.22) is prone to misdiagnosis or missed diagnosis. The combined application of chromosome karyotype analysis (G+C banding), copy number variation analysis, and FISH detection in clinical practice can accurately diagnose fetuses with psu idic(Y).</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"360-367"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079751","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":"[A case of complex structural variants in the Xq28 region diagnosed by whole genome sequencing].","authors":"Yulai Yang, Chuang Li, Ming Gao, Yuan Lyu","doi":"10.3760/cma.j.cn511374-20250217-00082","DOIUrl":"10.3760/cma.j.cn511374-20250217-00082","url":null,"abstract":"<p><strong>Objective: </strong>To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing (CNV-seq) through whole genome sequencing (WGS).</p><p><strong>Methods: </strong>A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject. WGS was carried out for the fetus and its parents. Bioinformatic software was used to analyze the chromosomal structure and CNVs. Quantitative PCR (qPCR) was applied to determine the expression level of the MECP2 gene. This study has been approved by the Ethics Committee of Shengjing Hospital (Ethic No. 2013PS33K).</p><p><strong>Results: </strong>A duplication (ChrX:153302641_153503563) and four breakpoints were identified on the X chromosome of the fetus' father. Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5'-UTR of the MECP2 gene, which was inserted into the Xp11 region. Additionally, an inversion was detected in the Xp11 region adjacent to the duplicated segment. RT-PCR results showed normal level of MECP2 mRNA expression. The Xq28 duplication has not encompassed the entire MECP2 gene, nor disrupted its structure or altered its expression.</p><p><strong>Conclusion: </strong>WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"355-359"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081177","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 an individual with Lan-negative rare blood group due to variant of ABCB6 gene].","authors":"Xianguo Xu, Kairong Ma, Ying Liu, Xiaozhen Hong, Yanling Ying, Faming Zhu","doi":"10.3760/cma.j.cn511374-20240710-00382","DOIUrl":"10.3760/cma.j.cn511374-20240710-00382","url":null,"abstract":"<p><strong>Objective: </strong>To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.</p><p><strong>Methods: </strong>A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband's clinical data. The proband's erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband's blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).</p><p><strong>Results: </strong>The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband's serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e.g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum.</p><p><strong>Conclusion: </strong>This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"286-291"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081191","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 feature and genetic analysis of a preterm infant with Netherton syndrome due to variants of SPINK5 gene].","authors":"Lingling Hu, Canyang Zhan, Mingyu Han, Tianming Yuan, Lihua Chen","doi":"10.3760/cma.j.cn511374-20240823-00453","DOIUrl":"10.3760/cma.j.cn511374-20240823-00453","url":null,"abstract":"<p><strong>Objective: </strong>To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).</p><p><strong>Methods: </strong>A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01).</p><p><strong>Results: </strong>The infant was born prematurely at 35⁺³ weeks due to \"premature rupture of membranes for 4 hours\" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father.</p><p><strong>Conclusion: </strong>This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"330-335"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081193","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":"[Progress in research on syndromic deafness associated with variants of CREBBP gene].","authors":"Mingjing Liang, Xiuhong Pang","doi":"10.3760/cma.j.cn511374-20241120-00608","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20241120-00608","url":null,"abstract":"<p><p>CREBBP gene encodes the transcriptional co-activator CREB-binding protein. This protein can participate in cell growth, differentiation and development through a variety of signal transduction pathways. Variants in this gene may cause syndromic deafness by affecting signal transduction pathways and development of skeletal and nervous systems. This review has summarized the structure and function of the CREBBP gene and the pathogenetic mechanism of syndromic deafness caused by CREBBP gene variants, with an aim to provide a basis for clinical diagnosis and treatment.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"368-374"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080024","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":"[Diversity of the Duffy blood group gene among ethnic Hui population in Henan Province].","authors":"Wenyan Cui, Hecai Yang, Cunquan Kong, Yongkui Kong, Yunfei You, Yujing Liu, Jinhua Liu, Maocai Chen, Yulin Zhang","doi":"10.3760/cma.j.cn511374-20241227-00689","DOIUrl":"10.3760/cma.j.cn511374-20241227-00689","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the diversity of Duffy blood group gene among ethnic Hui population from Henan Province using PacBio long-read sequencing technique.</p><p><strong>Methods: </strong>Randomly select 30 individuals with three generations of Hui ancestry from Henan as the study subjects. Full-length sequences of the Duffy blood group gene were obtained through PacBio long-read sequencing. Distribution of the predicted phenotype and genotype frequency were determined, and the linkage between Duffy haplotypes and variation sites was analyzed. Genetic diversity, natural selection pressure, and population genetic characteristics were evaluated. This study was approved by the Second Affiliated Hospital of Zhengzhou University (Ethics No. 2022223).</p><p><strong>Results: </strong>The predicted Duffy blood group phenotype in the Henan Hui population was predominantly Fy(a+b-). Three novel SNPs in the FY*01 allele were identified, with a total frequency of 13.33%, among which FY*01.NEW1 (c.199C>T) was the most common. A total of 32 variant sites were identified, with 28 located in intronic regions, indicating that genetic diversity was primarily concentrated in introns. The Duffy blood group gene was under negative selection pressure (dN/dS < 1, Tajima's D, Fu and Li's D* and F* significantly deviated from 0), suggesting overall conservation. The allele frequencies of Duffy blood group in the Henan Hui population was similar to that of the Xinjiang Hui, Xinjiang Kazakh, Inner Mongolia Mongolian, and Yuncheng Han populations, but significantly different from those of most Han and other ethnic groups (P < 0.05).</p><p><strong>Conclusion: </strong>This study revealed the characteristics of the Duffy blood group gene among the Henan Hui population and demonstrated the significant advantages of PacBio long-read sequencing technique in haplotype analysis, genetic diversity study, and novel mutation identification.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"274-281"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081195","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 pedigree affected with Distal arthrogryposis type 5D due to compound heterozygous variants of ECEL1 gene].","authors":"Weiyu Hu, Baiyun Chen, Yang Gao, Xiaona Wang, Yuke Li, Qianying Li, Huichun Zhang, Chao Gao","doi":"10.3760/cma.j.cn511374-20240114-00042","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240114-00042","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To explore the clinical phenotypes and genetic characteristics of a pedigree with Distal arthrogryposis type 5D (DA5D) caused by compound heterozygous variants in the ECEL1 gene.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A child (proband) diagnosed with DA5D and his family members (proband's parents and sister) who was admitted to the Department of Rehabilitation Medicine of Henan Children's Hospital in July 2022 due to \"multiplex distal arthrogryposis\" were enrolled into this study. Clinical data of the proband were collected and peripheral blood samples were obtained from the proband and members of his family about 3 mL. Trio-whole genome sequencing (trio-WGS) was carried out to detected the genetic variations of the proband and his family members. The candidate's pathogenic gene variants were screened and analyzed by Genome Aggregation Database (gnomAD) and other databases. The screened variants were annotated for clinical phenotypes using databases like the Online Mendelian Inheritance in Man (OMIM). The pathogenicity of the candidate variants was predicted by bioinformatics tools such as Provean. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), pathogenicity ratings were conducted for variant sites. The protein conservation and mutation structure prediction of ECEL1 protein among species were carried out though MEGA-X and PyMOL. The research protocol of this study was reviewed by the Ethics Committee of Henan Provincial Children's Hospital (Approval No. 2023-H-H01), and informed consent for clinical research was obtained from the guardians of the probands.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The proband had multiplex distal arthrogryposis involving hands, feet, knees, and ankles, and had right ptosis, micrognathia, low auricular position, and upturned nose. The parents and sister both had normal phenotypes. Trio-WGS and Sanger sequencing revealed that the child had compound heterozygous variants of paternal c.1742_c.1743insT and maternal c.2314T&gt;G, for which the father and sister were carriers of the c.1742_c.1743insT heterozygous variant and the mother was carrier of c.2314T&gt;A. Neither mutation site has been reported. According to guidelines of ACMG, the c.1742_c.1743insT variant was classified as likely pathogenic (PSV1+PM2_Supporting), and c.2314T&gt;G was classified as uncertain (PM2_Supporting+PM3+PP3). The results of conserved analysis of amino acid residue sequences of ECEL1 protein showed that the missense mutation of the maternal c.2314T&gt;G (p.Cys772Gly) was highly conserved among humans and other seven species. The protein structure prediction revealed that the c.1742_c.1743insT frameshift mutation led to the protein truncation, and the c.2314T&gt;G missense mutation resulted in the failure of forming 1 disulfide bond.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The compound heterozygous variants of ECEL1 gene were considered to be pathogenic for this DA5D patient, which have expanded the mu","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"322-329"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081190","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":"[Association between maternal age and chromosomal status of pre-implantation embryos].","authors":"Chunyan Wei, Rong Li, Changlong Xu, Ni'na Li, Ying Huang, Jian Zhang, Qiuwen Shi","doi":"10.3760/cma.j.cn511374-20240803-00421","DOIUrl":"https://doi.org/10.3760/cma.j.cn511374-20240803-00421","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the chromosome status of pre-implantation embryos from women of different ages, and assess the impact of age on it.</p><p><strong>Methods: </strong>A retrospective analysis was carried out on the results of PGT-A and PGT-M+PGT-A cycles by whole-genome amplification followed by next generation sequencing at the Second People's Hospital of Nanning between July 2021 and November 2023. The embryos were divided into five groups based on the women's age: ≤ 30 years old group, 31 ~ 34 years old group, 35 ~ 37 years old group, 38 ~ 40 years old group, and ≥ 41 years old group.The chromosomal status of embryos for each group was compared. This study has been approved by the Ethic Committee of the Hospital (Ethics No. Y2024312A).</p><p><strong>Results: </strong>This study has involved 390 couples and 436 PGT cycles, with a total of 1 651 blastocysts biopsied and analyzed. Among these, 835 embryos (50.6%) were found to have chromosomal abnormalities, including 490 (29.7%) with aneuploidies, 154 (9.3%) with chromosomal segment abnormalities, and 264 (16.0%) with chromosome mosaicisms. After adjusting the dosages of Gn, female BMI, male age, PGT indications, infertility type, LH, AMH and other parameters, maternal age appeared to be an independent factor for chromosomal abnormalities and aneuploidies in blastocysts (OR = 1.132, 95%CI = 1.089-1.177, P < 0.001; OR = 1.250, 95%CI = 1.188-1.315, P < 0.001). With the increase in female age, embryonic chromosome abnormalities have significantly increased in each group, with the rates being 32.3% (126/390), 43.1% (189/439), 45.1% (116/257), 66.3% (250/377), and 81.9% (154/188) (P < 0.001). Chromosomal aneuploidies have also significantly increased, with the rates being 8.2% (32/390), 16.6% (73/439), 24.5% (63/257), 49.6% (187/377), and 71.8% (135/188) (P < 0.001). The proportion of embryos with ≥ 2 chromosome abnormalities also significantly increased in abnormal embryos, with the rates being 28.6% (36/126), 30.2% (57/189), 39.7% (46/116), 48.4% (121/250), and 64.9% (100/154) (P < 0.001). Of note, the female age did not affect the prevalence of chromosomal segment abnormalities and mosaicisms (all P > 0.05).</p><p><strong>Conclusion: </strong>Above findings suggested that along with the increase in female age, there is an increase in the rate and complexity of chromosomal abnormalities, which may contribute to infertility in women with elder age.</p>","PeriodicalId":39319,"journal":{"name":"中华医学遗传学杂志","volume":"42 3","pages":"257-263"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081180","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}