Molecular Genetics & Genomic Medicine最新文献_第2页

A Novel TP63 Missense Mutation in the Sumoylation Motif Causes Isolated Split-Hand/Foot Malformation 4: A Pedigree Report and Literature Review. summoylation基序中一个新的TP63错义突变导致分离的手/足畸形4：系谱报告和文献综述。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70140

Wei Yang, Jian Zhou, Nuo Si, Xue Zhang

{"title":"A Novel TP63 Missense Mutation in the Sumoylation Motif Causes Isolated Split-Hand/Foot Malformation 4: A Pedigree Report and Literature Review.","authors":"Wei Yang, Jian Zhou, Nuo Si, Xue Zhang","doi":"10.1002/mgg3.70140","DOIUrl":"10.1002/mgg3.70140","url":null,"abstract":"Background: Heterozygous TP63 mutations cause a spectrum of disorders including split-hand/foot malformation 4 (SHFM4) and ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC3). While some SHFM4 mutations concurrently induce EEC3-like phenotypes (designated SHFM4/EEC3 mutations), their prevalence and distribution-particularly those near the p63 C-terminus-remain poorly characterized.Method: A multigenerational Chinese family with an isolated form of SHFM was investigated. Genetic analysis included real-time quantitative PCR and Sanger sequencing. Disease mutation databases and literature were systematically reviewed to identify all reported TP63 mutations causing isolated SHFM4 and to classify these mutations by clinical phenotypes.Results: We identified a novel likely pathogenic variant (NM_003722.5: c.2032G>C, p.E678Q) within a sumoylation motif near the C-terminus of p63. Analysis of 72 families (182 carriers) revealed 28 SHFM4-causing TP63 mutations, comprising 12 dual-phenotype SHFM4/EEC3 mutations and 16 isolated SHFM4-only mutations. Certain clinical traits of SHFM4 mutations and distribution characteristics for SHFM4-only mutations were observed.Conclusions: This study expands the SHFM4 mutation spectrum, demonstrating significant overlap between SHFM4 mutations and EEC3 mutations. The p.E678Q represents the most reliable SHFM4-only mutation near the protein C-terminus. These findings will improve molecular classification and genetic counseling for TP63-related disorders.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70140"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical Characteristics and Identification of Pathogenic Variant in a Large Chinese Family With Waardenburg Syndrome. 中国华登堡综合征大家族的临床特征及致病变异鉴定。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70134

Fei Hou, Yan Li, Luquan Cao, Yan Zhao, Shan Shan, Hua Jin

{"title":"Clinical Characteristics and Identification of Pathogenic Variant in a Large Chinese Family With Waardenburg Syndrome.","authors":"Fei Hou, Yan Li, Luquan Cao, Yan Zhao, Shan Shan, Hua Jin","doi":"10.1002/mgg3.70134","DOIUrl":"https://doi.org/10.1002/mgg3.70134","url":null,"abstract":"Background: Waardenburg syndrome is a genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. This study aims to explore the pathogenic variant in a large Waardenburg syndrome family and provide a theoretical basis for prenatal diagnosis of related family members.Methods: The clinical phenotype of the family members was analyzed. DNA was extracted from collected peripheral blood samples, and then exome sequencing and Sanger sequencing were performed. The pathogenicity of the genetic variant was evaluated by bioinformatics analysis. Amniocentesis was performed on the proband's mother (III13) to collect amniotic fluid samples for prenatal diagnosis.Results: There were 13 patients in the family. Most of the patients presented with deafness and abnormal pigmentation of hair or eyes, which was consistent with the diagnosis of Waardenburg syndrome type 2. Exome sequencing revealed a heterozygous variant of the SOX10 gene (NM_006941.4: c.386T>C (p.Leu129Pro)) in the proband. Sanger sequencing showed that the variant co-segregated with the disorder in this family. This variant has not been previously reported in relevant databases. The site p.Leu129 was highly conserved among various species and was important for protein structure and function.Conclusion: In this study, we reported a family with autosomal dominant Waardenburg syndrome type 2 and identified a heterozygous variant of the SOX10 gene by exome sequencing. In addition, prenatal diagnosis and genetic counseling were provided to the family related individual.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70134"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Variants in Four Families With Inherited Eye Disorders by Whole Exome Sequencing. 用全外显子组测序鉴定四个遗传性眼病家族的变异。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70141

Afeefa Jarral, Rabia Basharat, Sundus Sajid, Kinza Arshad, Imran Ali, Muhammad Ansar

{"title":"Identification of Variants in Four Families With Inherited Eye Disorders by Whole Exome Sequencing.","authors":"Afeefa Jarral, Rabia Basharat, Sundus Sajid, Kinza Arshad, Imran Ali, Muhammad Ansar","doi":"10.1002/mgg3.70141","DOIUrl":"10.1002/mgg3.70141","url":null,"abstract":"Background: Inherited eye disorders are a significant cause of vision loss worldwide. According to the World Health Organization (WHO) estimates approximately 2.2 billion people have some degree of vision loss, but a significant proportion of these are blind since early childhood. Due to poor infrastructure for genetic diagnosis, many affected families remain genetically unexplained in underdeveloped countries, including Pakistan.Methods: In this study, we utilized homozygosity mapping and exome sequencing to identify the genetic basis of the vision loss in four Kashmiri families that were presented with different types of eye disorders. We also performed quantitative reverse transcriptase-PCR (qRT-PCR) and measured the relative mRNA abundance of ALMS1 in blood cells of patients, carrier parents, and a healthy control.Results: Genetic analysis identified a novel homozygous 4 base pair frameshift deletion c.5747_5750del; p.(Ala1916Glufs*21) in ALMS1 in a family affected with Alstrom syndrome (AS), and already known variants were identified (CNGA3; c.1315C>T; p.(Arg439Trp) and FYCO1; c.2206C>T; p.(Gln736*) and c.3150 + 1G>T; p.(?)) in the remaining three families. The variant identified in the ALMS1 gene is predicted to activate nonsense mediated mRNA decay (NMD). Comparison of relative mRNA abundance of ALMS1 in patient-specific cells harboring c.5747_5750del negates the NMD activation. The results indicated the absence of NMD in patient-derived cells and therefore support the formation of a truncated ALMS1 protein in the patients with the c.5747_5750del variant.Conclusions: We expanded the mutation spectrum of ALMS1 but identified known variants in FYCO1 and CNGA3 genes. We also compiled the currently known mutations in these genes to establish genotype-phenotype correlation.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70141"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association Between KLF1, BCL11A and HBS1L-MYB Polymorphisms and Phenotypes With β-Thalassemia Patients in Hainan. 海南β-地中海贫血患者KLF1、BCL11A和HBS1L-MYB多态性和表型的相关性研究

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70142

Junjie Hu, Huaye Chen, Wei Gong, Min Feng, Shidong Fu, Weihua Xu, Zhichao Ma, Shengmiao Fu, Xinping Chen

{"title":"Association Between KLF1, BCL11A and HBS1L-MYB Polymorphisms and Phenotypes With β-Thalassemia Patients in Hainan.","authors":"Junjie Hu, Huaye Chen, Wei Gong, Min Feng, Shidong Fu, Weihua Xu, Zhichao Ma, Shengmiao Fu, Xinping Chen","doi":"10.1002/mgg3.70142","DOIUrl":"10.1002/mgg3.70142","url":null,"abstract":"Background: The factors influencing the phenotypic heterogeneity of patients with β-thalassemia have been receiving much attention in the field of hematology research. Activating the sustained expression of fetal hemoglobin (HbF) has proven to be one of the effective ways to alleviate the clinical symptoms of β-thalassemia. Studies have reported that single nucleotide polymorphisms (SNP) in KLF1, BCL11A, and HBS1L-MYB can increase the expression level of HbF in patients with β-thalassemia and have an impact on the phenotype.Methods: In this study, SNaPshot and Sanger sequencing were used to detect SNPs of BCL11A, HBS1L-MYB, and KLF1 in patients with different types of β-thalassemia collected in Hainan. Linkage disequilibrium and haplotype analysis were performed on mutant sites.Results: As a result, 41 mutation types of the above genes were detected (high mutation frequency and wide distribution range), and there was strong linkage disequilibrium at multiple mutation sites, resulting in multiple haplotypes. However, there are no significant differences in the distribution of gene polymorphisms between different types of β-thalassemia, suggesting that the modifications of KLF1, BCL11A, and HBS1L-MYB may have little impact on the β-thalassemia phenotype in this region.Conclusion: Our study provides data support for assessing the impact of modified genes on the phenotype of patients with β-thalassemia in Hainan, and also promotes the clinical accurate diagnosis and classification evaluation of β-thalassemia.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70142"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosomal Abnormalities in Couples Experiencing Recurrent Implantation Failure in West of Iran: A Case-Control Study. 在伊朗西部经历反复植入失败的夫妇染色体异常：一项病例对照研究。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70137

Atefeh Asgari, Amir Mohammad Salehi, Fatemeh Shahbazi, Safieh Ghahremani, Ebrahim Kamrani Saleh

{"title":"Chromosomal Abnormalities in Couples Experiencing Recurrent Implantation Failure in West of Iran: A Case-Control Study.","authors":"Atefeh Asgari, Amir Mohammad Salehi, Fatemeh Shahbazi, Safieh Ghahremani, Ebrahim Kamrani Saleh","doi":"10.1002/mgg3.70137","DOIUrl":"10.1002/mgg3.70137","url":null,"abstract":"Background: Recurrent Implantation Failure (RIF) is defined as the inability to establish pregnancy despite high-quality embryo transfer after the application of at least three consecutive in vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer procedures. Chromosomal abnormalities are one of the primary reasons for pregnancy failure, miscarriage, and birth defects in both natural conception and IVF pregnancies. This study was to evaluate the incidence of chromosomal abnormalities in peripheral blood samples from 100 couples who experienced RIF.Methods: Chromosomal structure analysis was conducted on peripheral blood samples from 100 couples who experienced RIF between 2018 and 2022. Additionally, cytogenetic assessments were conducted on 200 healthy individuals without clinical issues to ensure the accuracy. The GTG-Banding technique was employed in our research.Results: Out of the 200 individuals who faced RIF, six (3%) exhibited chromosomal abnormalities, comprising five (83.3%) men and one (16.6%) woman. Translocation was the main type of autosomal structural abnormalities; also, we found one inversion and one pstk - (population polymorphism). Conversely, no chromosomal abnormalities were detected in the control group. We found chromosomal abnormalities in 3% of study participants who had experienced RIF.Conclusion: Chromosomal abnormalities significantly contribute to RIF. Therefore, it is imperative to conduct cytogenetic screening for both partners before initiating any assisted reproductive technology procedures.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70137"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

De Novo GLI2 Missense Variant in a Child With Isolated Hypopituitarism and Craniofacial Anomalies: Expanding the Phenotypic Spectrum. 孤立垂体功能减退和颅面异常儿童的新生GLI2错义变异：扩大表型谱。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70136

Himanshu Goel, Katrina Harrison

{"title":"De Novo GLI2 Missense Variant in a Child With Isolated Hypopituitarism and Craniofacial Anomalies: Expanding the Phenotypic Spectrum.","authors":"Himanshu Goel, Katrina Harrison","doi":"10.1002/mgg3.70136","DOIUrl":"10.1002/mgg3.70136","url":null,"abstract":"Background: Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, postaxial polydactyly, and craniofacial anomalies, associated with pathogenic GLI2 variants. Genotype-phenotype correlations suggest missense variants may present with isolated pituitary phenotypes.Methods: We evaluated an 8-year-old boy referred for short stature, failure to thrive, and neurodevelopmental concerns. Clinical assessment, endocrine evaluation, imaging studies, and trio exome sequencing were performed.Results: The patient exhibited growth hormone deficiency, dolichocephaly, midline diastema, lip and tongue ties, hypotonia, and ADHD. No polydactyly was noted. Trio exome sequencing revealed a de novo heterozygous likely pathogenic GLI2 variant (c.1496G>T; p.Arg499Leu) located within the DNA-binding zinc finger domain.Conclusion: This case expands the phenotypic spectrum of GLI2-related disorders and reinforces that non-truncating GLI2 variants are often associated with isolated hypopituitarism and subtle craniofacial or neurodevelopmental features. Genomic testing should be considered in similar clinical presentations.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70136"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frequency and Spectrum of Actionable Secondary Findings in the Maltese Population. 马耳他人群中可操作的次要发现的频率和频谱。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-09-01 DOI: 10.1002/mgg3.70143

Laura Grech, Celine Ann Grech, Jasmine Spiteri, Dillon Mintoff, Nikolai Paul Pace

{"title":"Frequency and Spectrum of Actionable Secondary Findings in the Maltese Population.","authors":"Laura Grech, Celine Ann Grech, Jasmine Spiteri, Dillon Mintoff, Nikolai Paul Pace","doi":"10.1002/mgg3.70143","DOIUrl":"10.1002/mgg3.70143","url":null,"abstract":"Background: The identification of actionable secondary findings (SFs) through clinical exome sequencing has become increasingly relevant with the integration of genomics into routine healthcare. The frequency and spectrum of these findings vary across populations.Methods: We analyzed exome sequencing data from 350 unrelated Maltese individuals, comprising 320 pseudonymised controls and 30 participants from the pilot sequencing phase of the national biobank DwarnaBio, to assess the prevalence of pathogenic or likely pathogenic (P/LP) variants in the ACMG SF v3.2 gene list. All samples underwent uniform sequencing, rigorous quality control, and variant interpretation according to ACMG/AMP guidelines.Results: Actionable P/LP variants were identified in 12 individuals (3.4%) across autosomal dominant genes, predominantly associated with inherited cardiac conditions and cancer predisposition syndromes. These findings highlight the importance of including underrepresented populations in genomic research and emphasize the need to establish provisions for the return of clinically actionable results to biobank participants, supported by access to genetic counseling.Conclusion: Our results advocate for the integration of population-specific genomic data into national precision medicine frameworks, particularly for small or isolated populations where tailored approaches to variant curation and clinical translation are required. This study provides the first baseline estimate of actionable SFs in the Maltese population and offers insights for advancing precision medicine frameworks.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 9","pages":"e70143"},"PeriodicalIF":1.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Prenatal Ultrasound Study of Cerebral Cortical Sulci and Gyri Development in Fetuses With Overgrowth Syndrome and/or Cerebral Malformations due to Abnormalities in MTOR Pathway Genes. MTOR通路基因异常导致的过度生长综合征和/或大脑畸形胎儿大脑皮质沟和脑回发育的产前超声研究

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-08-01 DOI: 10.1002/mgg3.70130

Hui Wang, Shengli Li, Qiong Zhen, Huaxuan Wen, Bingguang Liu, Liyuan Chen, Yang Liu, Caiqun Luo, Xiaoxia Wu

{"title":"A Prenatal Ultrasound Study of Cerebral Cortical Sulci and Gyri Development in Fetuses With Overgrowth Syndrome and/or Cerebral Malformations due to Abnormalities in MTOR Pathway Genes.","authors":"Hui Wang, Shengli Li, Qiong Zhen, Huaxuan Wen, Bingguang Liu, Liyuan Chen, Yang Liu, Caiqun Luo, Xiaoxia Wu","doi":"10.1002/mgg3.70130","DOIUrl":"10.1002/mgg3.70130","url":null,"abstract":"Objectives: To investigate the abnormal development of cerebral cortical sulci and gyri in fetuses with Overgrowth Syndrome and/or Cerebral Malformations Due to mTOR Pathway Gene Abnormalities (OCMMPG), focusing on prenatal imaging correlates of mTOR dysregulation.Methods: Retrospective analysis of three OCMMPG cases diagnosed via whole-exome sequencing (WES). Sulco-gyral morphology was assessed using 2D cross-sectional imaging and 3D inversion Crystalvue/Realisticvue (3D-ICRV) rendering.Results: Polymicrogyria (PMG) was identified in all cases via 2D and 3D-ICRV imaging. The third fetus exhibited a malformed Sylvian fissure and hypoplastic parieto-occipital sulcus (POS). 3D-ICRV revealed cortical thickening and microgyral fusion, aligning with PMG criteria.Conclusions: The integration of 2D imaging and 3D-ICRV technology enables comprehensive prenatal assessment of sulco-gyral development. Our findings highlight the utility of this approach in detecting mTOR-related cortical dysplasias, particularly in cases with atypical Sylvian fissure or POS hypoplasia.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 8","pages":"e70130"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal Characterization of Houge-Janssens Syndrome Type 2: A Case Report and Systematic Review of Fetal Phenotypes Associated With PPP2R1A Mutations. Houge-Janssens综合征2型的产前特征：与PPP2R1A突变相关的胎儿表型的病例报告和系统回顾

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-08-01 DOI: 10.1002/mgg3.70129

Jiancheng Hu, Jialun Pang, Lin Zhou, Haiyan Kuang, Wenxian Yu, Ying Peng

{"title":"Prenatal Characterization of Houge-Janssens Syndrome Type 2: A Case Report and Systematic Review of Fetal Phenotypes Associated With PPP2R1A Mutations.","authors":"Jiancheng Hu, Jialun Pang, Lin Zhou, Haiyan Kuang, Wenxian Yu, Ying Peng","doi":"10.1002/mgg3.70129","DOIUrl":"10.1002/mgg3.70129","url":null,"abstract":"Background: Houge-Janssens syndrome type 2 (HJS2, OMIM 616362) is a rare neurodevelopmental disorder caused by pathogenic variants in PPP2R1A, typically characterized postnatally by hypotonia, developmental delay, intellectual disability, and distinctive craniofacial features.Methods: We describe a 28-year-old pregnant woman referred for increased nuchal translucency (4.4 mm) and high risk on first trimester screening. Noninvasive prenatal testing showed no common aneuploidies. At 23 weeks of gestation, fetal ultrasound revealed ventriculomegaly and suspected partial agenesis of the corpus callosum. Genetic testing included karyotyping, chromosomal microarray analysis (CMA), and trio-based whole exome sequencing (WES).Results: Karyotype and CMA were normal. WES identified a de novo heterozygous missense variant in PPP2R1A, NM_014225.6: c.548G>A (p.R183Q), classified as pathogenic. Following genetic counseling, the couple elected to terminate the pregnancy. Integrating our findings with 12 previously reported prenatal cases, we conducted a systematic review of fetal phenotypes associated with PPP2R1A variants. The most common features were ventriculomegaly (92%), agenesis or dysgenesis of the corpus callosum (50%), and congenital heart defects (42%).Conclusion: We present the most comprehensive synthesis to date of prenatal phenotypes associated with PPP2R1A-related neurodevelopmental disorders. These findings provide crucial insights into the prenatal spectrum of HJS2 and highlight key sonographic indicators to support early diagnosis and genetic counseling.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 8","pages":"e70129"},"PeriodicalIF":1.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atypical Prader-Willi Syndrome Deletions: Insights Into the Complex Regulation and Phenotypic Variability. 非典型Prader-Willi综合征缺失：对复杂调控和表型变异的见解。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2025-08-01 DOI: 10.1002/mgg3.70131

Jannis Buecking, Christian P Schaaf

引用次数: 0