Clinical Genetics最新文献

A Further Case Supporting CCNK as a Neurodevelopmental Disease Gene. 支持CCNK作为神经发育疾病基因的又一病例

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-16 DOI: 10.1111/cge.70093

Clara Xiol, Jonathan Olival, Loreto Martorell, Juan Darío Ortigoza-Escobar

引用次数: 0

Genetic and Clinical Spectrum of Osteogenesis Imperfecta in an Egyptian Cohort With a High Rate of Lethal Phenotypes. 具有高致死性表型的埃及队列中成骨不全的遗传和临床谱。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-15 DOI: 10.1111/cge.70091

Ghada Elhady, Asmaa K Amin, Asier Iturrate, Sara El-Dessouky, Julian Nevado, Belinda Campos-Xavier, Lova S Matsa, Cecilia Giunta, Pablo Lapunzina, Victor L Ruiz-Perez, Ebtesam Abdalla

{"title":"Genetic and Clinical Spectrum of Osteogenesis Imperfecta in an Egyptian Cohort With a High Rate of Lethal Phenotypes.","authors":"Ghada Elhady, Asmaa K Amin, Asier Iturrate, Sara El-Dessouky, Julian Nevado, Belinda Campos-Xavier, Lova S Matsa, Cecilia Giunta, Pablo Lapunzina, Victor L Ruiz-Perez, Ebtesam Abdalla","doi":"10.1111/cge.70091","DOIUrl":"https://doi.org/10.1111/cge.70091","url":null,"abstract":"Osteogenesis imperfecta (OI) is a genetically heterogeneous connective tissue disorder marked by bone fragility and deformities. This study aimed to define the clinical and molecular characteristics of 21 OI patients from 15 unrelated Egyptian families. Most probands were analyzed by exome sequencing. In three consanguineous cases, variants were identified through SNP array-based homozygosity mapping followed by direct sequencing of a candidate gene. Genotype-phenotype correlations were additionally explored. Parental consanguinity was documented in 66.7% (10/15) of the total cohort and in 100% (8/8) of the families with autosomal recessive OI. Pathogenic or likely pathogenic variants were identified in 14 families, five of which were novel. A variant of uncertain significance was identified in the remaining family. COL1A1 and COL1A2 (n = 7) were the most commonly mutated genes, followed by CRTAP (n = 4), while variants in P3H1, WNT1, CREB3L1, and SEC24D were each identified in a single patient. The present study highlights the molecular heterogeneity of OI. In total, 15 distinct variants in seven OI-related genes were identified. We also report a particularly high number of OI lethal forms affecting 10 patients out of 21. The study adds further evidence for the utility of ES in the genetic diagnosis of OI, which facilitates counseling and personalized care.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ApoE Polymorphism Analysis in Health and Disease of South Asian Populations: A Systematic Review and Meta-Analysis. 南亚人群健康和疾病中的载脂蛋白e多态性分析：系统回顾和荟萃分析

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-13 DOI: 10.1111/cge.70064

Prayash Paudel, Asutosh Sah, Poonam Paudel

{"title":"ApoE Polymorphism Analysis in Health and Disease of South Asian Populations: A Systematic Review and Meta-Analysis.","authors":"Prayash Paudel, Asutosh Sah, Poonam Paudel","doi":"10.1111/cge.70064","DOIUrl":"https://doi.org/10.1111/cge.70064","url":null,"abstract":"This systematic review and meta-analysis assesses the distribution and health implications of apolipoprotein E (ApoE) ε2, ε3, and ε4 alleles, which play crucial roles in lipoprotein metabolism, in South Asian populations, with a focus on neurodegenerative diseases, movement disorders, traumatic brain injury, mental health disorders, cardiovascular disorders, metabolic disorders, and trauma-related disorders. A total of 53 studies identified through comprehensive searches in PubMed, Embase, and Google Scholar up to July 31, 2024, were included on the basis of predefined eligibility criteria after Risk of Bias Assessment via the New York Ottawa Scale. ε3/ε3 was found to be the most prevalent genotype, followed by ε3/ε4 and ε2/ε3. ε4-containing genotypes were associated with susceptibility to Alzheimer's disease, coronary artery disease, vascular dementia, and obesity, though high heterogeneity in some associations necessitates cautious interpretation, whereas the ε2/ε3 and ε2 alleles showed protective effects in some conditions. These studies had several limitations, including data gaps for specific health conditions, underrepresentation of some South Asian countries, and heterogeneity in outcomes. Despite gaps in the data for some countries and specific health conditions, this review reveals distinct South Asian patterns in ApoE polymorphism-disease associations, highlighting the need for targeted genetic research and tailored public health strategies to advance personalized medicine and healthcare policies in this region. There was no specific funding for this study. The study was registered in PROSPERO (registration number CRD42024575197).","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic Landscape of Robin Sequence: A Systematic Review. 罗宾序列的遗传景观：系统综述。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-12 DOI: 10.1111/cge.70088

Shirley van de Velde, Aebele B Mink van der Molen, Augusta M A Lachmeijer, Daan de Leijer, Jeroen J Smits, Maarten P G Massink, Sarah L Versnel, Marie-José H van den Boogaard, Emma C Paes

{"title":"Genetic Landscape of Robin Sequence: A Systematic Review.","authors":"Shirley van de Velde, Aebele B Mink van der Molen, Augusta M A Lachmeijer, Daan de Leijer, Jeroen J Smits, Maarten P G Massink, Sarah L Versnel, Marie-José H van den Boogaard, Emma C Paes","doi":"10.1111/cge.70088","DOIUrl":"https://doi.org/10.1111/cge.70088","url":null,"abstract":"Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis, and upper airway obstruction, often occurring with cleft palate and syndromic conditions. The genetic basis of RS is heterogeneous, including monogenic variants and chromosomal rearrangements. This systematic review synthesizes the current genetic landscape of RS, analyzing data from 107 studies that employed various genetic testing methods, including chromosomal microarray (CMA), targeted sequencing, and whole exome sequencing (WES). A distinction is made between genetic variants identified in isolated versus non-isolated RS. Pathogenic variants in genes as SOX9, SNRPB, SATB2, TGDS, RBM10, COL11A1, and COL2A1 are frequently identified, many of which are linked to non-isolated RS. The most common chromosomal aberrations are deletions of 22q11.2 and 18q. Up-to-date genetic testing is essential to enable accurate diagnosis and personalized clinical care. With the growing use of whole genome sequencing (WGS) in clinical practice, the need for phenotype-driven interpretation tools is increasing. Some platforms can prioritize gene relevance based on Human Phenotype Ontology (HPO) terms. Documenting both known and novel RS-associated genes is therefore crucial to fully realize the diagnostic potential of WGS and support evidence-based clinical decision-making.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Founder Variants of the Turkish. 土耳其语的创始人变体。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-11 DOI: 10.1111/cge.70080

Ahmet Kablan

引用次数: 0

Genotype-Phenotype Correlations in Chinese Pediatric Patients With Single Large-Scale Mitochondrial DNA Deletion Disorders. 中国儿童单大规模线粒体DNA缺失症的基因型-表型相关性

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-11 DOI: 10.1111/cge.70089

Jun Wang, Minhan Song, Zhimei Liu, Chaolong Xu, Ying Zou, Xin Duan, Yang Liu, Weihua Zhang, Jiuwei Li, Fang Fang

{"title":"Genotype-Phenotype Correlations in Chinese Pediatric Patients With Single Large-Scale Mitochondrial DNA Deletion Disorders.","authors":"Jun Wang, Minhan Song, Zhimei Liu, Chaolong Xu, Ying Zou, Xin Duan, Yang Liu, Weihua Zhang, Jiuwei Li, Fang Fang","doi":"10.1111/cge.70089","DOIUrl":"https://doi.org/10.1111/cge.70089","url":null,"abstract":"This study investigated clinical and genetic characteristics of Chinese pediatric patients with single large-scale mitochondrial DNA deletions (SLSMD). We analyzed 28 patients (July 2004-March 2025) using long-range PCR and next-generation sequencing. Spearman correlation and ANOVA assessed genotype-phenotype relationships. Patients (mean age 5.52 ± 3.96 years) exhibited multi-organ involvement (5.43 ± 1.87 organs). Common initial presentations included ocular (29%), neurologic, and endocrine dysfunction. Only 14.3% had the classic 4977 bp deletion, and 23 novel deletions were identified in 25 patients. Larger deletions correlated with more deleted MRC complexes (r = 0.516, p = 0.0123) and more deleted tRNAs (r = 0.534, p = 0.0103). Kearns-Sayre syndrome (KSS) patients had later onset (p = 0.0337), larger deletions (p = 0.0263), and greater tRNA/MRC complex (p = 0.0263, p = 0.0319) involvement than non-KSS patients. SLSMD in Chinese children primarily causes KSS, Pearson syndrome (PS), and progressive ophthalmoplegia with multi-organ involvement. Genotype-phenotype correlations exist, particularly between deletion size, onset age, and disease severity. KSS patients show distinct genetic and clinical profiles, suggesting slower progression. This study expands the known SLSMD spectrum and underscores mitochondrial testing in pediatric multi-organ disorders.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical Testing Promotes Interpretation of Variants of Uncertain Significance in Prenatal Genetic Disease Testing in Four Organic Acidurias. 生化检测促进了四种有机酸血症产前遗传病检测中不确定意义变异的解释。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-09 DOI: 10.1111/cge.70086

Kaili Yin, Qingwei Qi

引用次数: 0

Reduced Penetrance and Variable Expression of Dilated Cardiomyopathy Associated With Homozygous Truncating Variants in NRAP Gene. 与NRAP基因纯合截断变异相关的扩张型心肌病外显率降低和可变表达。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-10-01 DOI: 10.1111/cge.70078

Aisha Alqahtani, Sahar Tulbah, Nadiah Alruwaili, Saud Takroni, Maarab Alkorashy, Waleed Manea, Dimpna C Albert Brotons, Abdullah Alwadai, Jehad Alburaiki, Fowzan Alkuraya, Nadiah Al-Hashmi, Samah Zarroug, Zuhair N Al-Hassnan

{"title":"Reduced Penetrance and Variable Expression of Dilated Cardiomyopathy Associated With Homozygous Truncating Variants in NRAP Gene.","authors":"Aisha Alqahtani, Sahar Tulbah, Nadiah Alruwaili, Saud Takroni, Maarab Alkorashy, Waleed Manea, Dimpna C Albert Brotons, Abdullah Alwadai, Jehad Alburaiki, Fowzan Alkuraya, Nadiah Al-Hashmi, Samah Zarroug, Zuhair N Al-Hassnan","doi":"10.1111/cge.70078","DOIUrl":"https://doi.org/10.1111/cge.70078","url":null,"abstract":"Dilated Cardiomyopathy (DCM) is a genetically heterogeneous condition of left ventricular dilation and systolic dysfunction, leading to heart failure. It is mostly inherited in a dominant pattern. Recessive inheritance has been rarely encountered. This study aims to outline the clinical and genetic characteristics associated with recessively inherited NRAP truncating variants in our highly consanguineous population. Twenty-three cases from 12 unrelated consanguineous families were recruited. Cardiological evaluation and genetic testing with exome sequencing (ES) were conducted in all cases, followed by segregation analysis of first-degree relatives. Genetic analysis with ES identified five unique homozygous truncating variants in NRAP in the affected cases. The segregation analysis detected a total of 23 homozygous and 21 heterozygous individuals. Out of the total homozygous cases, three were asymptomatic, while 20 exhibited symptoms with remarkable inter- and intrafamilial variability of the age of onset (range: 9 months to 47 years, median 10 years), seven of whom died (range: 9 months to 28 years, median 7 years). None of the heterozygous individuals showed symptoms. Of note, three homozygous cases underwent heart transplantation. Our findings show that truncating variants in NRAP are associated with reduced penetrance and clinical variability, suggesting a complex mechanism beyond simple Mendelian inheritance.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Genetic Defects of N-DRC in Male Infertility. 男性不育症中N-DRC的遗传缺陷。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-29 DOI: 10.1111/cge.70081

Jiao Qin, Jinyu Wang, Dingming Li, Fuping Li

{"title":"The Genetic Defects of N-DRC in Male Infertility.","authors":"Jiao Qin, Jinyu Wang, Dingming Li, Fuping Li","doi":"10.1111/cge.70081","DOIUrl":"https://doi.org/10.1111/cge.70081","url":null,"abstract":"The nexin-dynein regulatory complex (N-DRC) is a large protein complex composed of at least 11 subunits (DRC1-DRC11) and plays a crucial role in ciliary and flagellar motility. It links adjacent doublets of microtubules (DMTs) between A and B microtubules, regulating dynein motor activity. Genetic defects in N-DRC subunits lead to primary ciliary dyskinesia (PCD) and abnormal flagellar motility. In recent years, an increasing number of genetic mutations in N-DRC subunits have been reported, associated with male infertility, characterized by multiple morphological abnormalities of the flagella (MMAF) and asthenozoospermia. Therefore, genetic diagnosis of N-DRC defects in male infertility is of significant clinical importance, impacting the reproductive health of patients and the well-being of their offspring. In this review, we summarize the gene mutations of N-DRC subunits reported in the literature concerning male infertility, analyze the phenotypes of affected patients, and outline the functions and mechanisms of N-DRC in sperm flagellar motility. Furthermore, we provide an overview of gene knockout (KO) mouse models of N-DRC and their associated phenotypes. Finally, we summarize the outcomes of assisted reproductive technology (ART) in both patients and KO mice, offering references for the diagnosis and treatment of clinical male infertility caused by N-DRC genetic factors.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical, Biochemical and Molecular Characterisation of Newborns With Fatty Acid β-Oxidation Disorders: Novel Variants in the ACADM, ACADVL and SLC22A5 Genes. 新生儿脂肪酸β氧化障碍的临床、生化和分子特征：ACADM、ACADVL和SLC22A5基因的新变异

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-29 DOI: 10.1111/cge.70083

Irene Hidalgo Mayoral, Amanda Herranz Cecilia, Carmen Rodríguez-Jiménez, Ana Carazo Álvarez, Ana Bergua Martínez, José David Andrade Guerrero, Ana Moráis López, Sonia Rodríguez-Nóvoa

{"title":"Clinical, Biochemical and Molecular Characterisation of Newborns With Fatty Acid β-Oxidation Disorders: Novel Variants in the ACADM, ACADVL and SLC22A5 Genes.","authors":"Irene Hidalgo Mayoral, Amanda Herranz Cecilia, Carmen Rodríguez-Jiménez, Ana Carazo Álvarez, Ana Bergua Martínez, José David Andrade Guerrero, Ana Moráis López, Sonia Rodríguez-Nóvoa","doi":"10.1111/cge.70083","DOIUrl":"https://doi.org/10.1111/cge.70083","url":null,"abstract":"In this study, we aimed to assess clinical, laboratory and molecular features of newborns with clinical suspicion for systemic primary carnitine deficiency (CUD), medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). The implementation of newborn screening programs for fatty acid β-oxidation disorders (FAODs) has changed the natural course of these diseases, facilitating the initiation of preventive or therapeutic measures for affected newborns shortly after birth. This study included 94 newborns who were admitted between 2016 and 2023 because of biochemical signs of CUD, MCADD and VLCADD, and provided clinical, biochemical and genotypic data. Definitive molecular diagnosis confirmed that 16/94 newborns (17%) were true positives of the NBS, and 17 novel variants were detected in SLC22A5, ACADM and ACADVL genes. We assessed the clinical evolution of patients over time. This study expands the genotypic spectrum of SLC22A5, ACADM and ACADVL and highlights the role of genetics in identifying and correctly characterising FAODs.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0