Clinical Genetics最新文献

Aarskog Syndrome: Deep Phenotyping and Genomic Landscape of a New Cohort Including Adult Patients.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-04-02 DOI: 10.1111/cge.14744

Gozde Tutku Turgut, Umut Altunoglu, Şahin Avcı, Tuğba Kalaycı, Ayça Dilruba Aslanger, Volkan Karaman, Zehra Oya Uyguner, Hülya Kayserili

{"title":"Aarskog Syndrome: Deep Phenotyping and Genomic Landscape of a New Cohort Including Adult Patients.","authors":"Gozde Tutku Turgut, Umut Altunoglu, Şahin Avcı, Tuğba Kalaycı, Ayça Dilruba Aslanger, Volkan Karaman, Zehra Oya Uyguner, Hülya Kayserili","doi":"10.1111/cge.14744","DOIUrl":"https://doi.org/10.1111/cge.14744","url":null,"abstract":"Aarskog-Scott syndrome (AAS, MIM#305400) is an X-linked disorder characterized by recognizable facial features, short stature, and genitourinary and skeletal malformations. AAS is attributed to pathogenic variants in FGD1, and ~60 patients with a genetic diagnosis have been reported to date. We hereby present a molecularly confirmed cohort of 14 male AAS patients from 13 families. Among 14 patients, 12 were referred during childhood, while two were referred at adulthood due to infertility. Six out of 11 patients with available records had antenatal manifestations, comprising shortened tubular bones, growth restriction, polyhydramnios, pes equinovarus, increased nuchal translucency, fetal hypokinesia, echogenic intracardiac focus, and ambiguous genitalia. In addition to well-described AAS findings, distinctive features observed in multiple patients included variable skin findings (n = 5), renal malformations (n = 2), muscular build (n = 2), and infertility (n = 2). Cardiac (n = 4) and ocular manifestations (n = 6) were identified at significantly higher rates than previously reported. This cohort also presents new patients with osteochondritis dissecans and oligo/azoospermia, providing further evidence to acknowledge these once-reported findings as part of the disease spectrum. Eleven different FGD1 variants, including seven novel ones, were identified through targeted FGD1 sequencing. Two variants were found to be recurrent, detected in two independent families. Our study provides additional insights into the clinical and genotypic landscape of AAS through the largest molecularly confirmed cohort, including two adult patients.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763237","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

Research-Based Whole Genome Sequencing Identifies Biallelic Loss of Function Variants in DOCK3 Gene Causing DOCK3-Related Disorder: The End of a Diagnostic Journey for This Family.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-28 DOI: 10.1111/cge.14741

Khurram Liaqat, Kayla Treat, Lili Mantcheva, Aaron McLaughlin, Amy Breman, Molly McPheron, Erin Conboy, Francesco Vetrini

{"title":"Research-Based Whole Genome Sequencing Identifies Biallelic Loss of Function Variants in DOCK3 Gene Causing DOCK3-Related Disorder: The End of a Diagnostic Journey for This Family.","authors":"Khurram Liaqat, Kayla Treat, Lili Mantcheva, Aaron McLaughlin, Amy Breman, Molly McPheron, Erin Conboy, Francesco Vetrini","doi":"10.1111/cge.14741","DOIUrl":"https://doi.org/10.1111/cge.14741","url":null,"abstract":"The DOCK3 gene (NM_004947.5) is located on chromosome 3p21.2 spanning 53 exons and encodes the dedicator of cytokinesis 3 protein. DOCK3 belongs to the family of guanine nucleotide exchange factors (GEFs) that activate GTPases. DOCK3 is expressed almost exclusively in the central nervous system and has been shown to promote axonal outgrowth. Biallelic disruptions of DOCK3 are implicated in a neurodevelopmental disorder presenting with intellectual disability, hypotonia and ataxia (OMIM: 618292). We report a 9-year-old female with global developmental delay, moderate intellectual disability, wide-based and ataxic gait, hypotonia, benign nocturnal myoclonus, bifid uvula, moderate obstructive sleep apnea, and alternating esotropia. Prior to enrollment in the Undiagnosed Rare Disease Clinic (URDC), the patient's clinical exome testing was negative. The subsequent enrollment in URDC allowed further research investigations through whole genome sequencing (GS) that identified two compound heterozygous variants in the DOCK3 gene, ultimately yielding an unequivocal definitive molecular diagnosis.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728833","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

Case Report: Gingival Hyperplasia and Scoliosis as Additional Features of EMC10-Related Neurodevelopmental Disorder.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-27 DOI: 10.1111/cge.14743

Gaëlle Forest-St-Onge, Jean-François Soucy, Marie-Ange Delrue, Philippe M Campeau

引用次数: 0

Presenting Characteristics and Medical Conditions in 67 Cases With Trisomy 9 Mosaicism.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-25 DOI: 10.1111/cge.14742

Deborah A Bruns

引用次数: 0

Large-Scale Analysis of the Thalassemia Mutation Spectrum in Guizhou Province, Southern China, Using Third-Generation Sequencing.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-17 DOI: 10.1111/cge.14729

Ying Zhang, Jiangfen Wu, Lingyan Ren, Fangfang Li, Xian Wu, Min Guo, Guiqin You, Zhengqian Fu, Guiping Long, Shengwen Huang

{"title":"Large-Scale Analysis of the Thalassemia Mutation Spectrum in Guizhou Province, Southern China, Using Third-Generation Sequencing.","authors":"Ying Zhang, Jiangfen Wu, Lingyan Ren, Fangfang Li, Xian Wu, Min Guo, Guiqin You, Zhengqian Fu, Guiping Long, Shengwen Huang","doi":"10.1111/cge.14729","DOIUrl":"https://doi.org/10.1111/cge.14729","url":null,"abstract":"This study aimed to comprehensively characterize the molecular spectrum of thalassemia by retrospectively analyzing genetic screening results from a large cohort of individuals. Peripheral blood samples were collected from 26 047 individuals seeking care at the Departments of Obstetrics and Gynecology, Pediatrics, Reproductive Medicine, and Hematology across multiple regional hospitals in Guizhou Province, China. Thalassemia gene mutations were analyzed using targeted third-generation sequencing (TGS) to assess the mutation spectrum in this population. Of the cohort, 5099 individuals were identified as thalassemia carriers, yielding an overall carrier rate of 19.58%. The carrier rates differed significantly between the southern and northern regions of Guizhou (p < 0.001). α-thalassemia included 40 distinct genotypes, β-thalassemia comprised 33 genotypes, and cases with concurrent α- and β-thalassemia mutations exhibited 47 unique genotypes. A total of 17 distinct mutations were identified in the α-thalassemia gene and 26 in the β-thalassemia gene. The mutation spectrum in Guizhou showed significant differences when compared to other southern Chinese populations, with notable regional variations within Guizhou itself. This study highlights the substantial genetic diversity and distinct mutation patterns of thalassemia in Guizhou Province. These findings provide valuable insights into the distribution of thalassemia genotypes and alleles, which can inform genetic counseling and prenatal screening strategies tailored to this population.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647439","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

Genotype-Phenotype Correlations, Treatment, and Prognosis of Children With Early-Onset (Neonatal) Marfan Syndrome.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-10 DOI: 10.1111/cge.14722

Eva C van der Leest, Annelies E van der Hulst, Gerard Pals, Lidiia Zhytnik, Lillian Lai, Caroline Jacquemart, Lindsay Mills, Michiel Houben, Petr Jira, Bert L Lunshof, Jessica Warnink-Kavelaars, Vivian de Waard, Leonie A Menke

{"title":"Genotype-Phenotype Correlations, Treatment, and Prognosis of Children With Early-Onset (Neonatal) Marfan Syndrome.","authors":"Eva C van der Leest, Annelies E van der Hulst, Gerard Pals, Lidiia Zhytnik, Lillian Lai, Caroline Jacquemart, Lindsay Mills, Michiel Houben, Petr Jira, Bert L Lunshof, Jessica Warnink-Kavelaars, Vivian de Waard, Leonie A Menke","doi":"10.1111/cge.14722","DOIUrl":"https://doi.org/10.1111/cge.14722","url":null,"abstract":"Early-onset Marfan syndrome (eoMFS) is a severe and rare form of Marfan syndrome characterized by severe atrioventricular valve insufficiency developing before or shortly after birth. It is unclear which factors (interventions and/or genotype) influence survival. Forty-one individuals with eoMFS with a fibrillin-1 gene (FBN1) variant in exon 24-32 (CRCh37) were included. At the last follow-up, 14/41 (34%) were alive (8 months-18 years) and 27/41 (66%) were deceased. Median age of death was 1 month and 88% of the deaths occurred before 5 months of age. More individuals alive past the age of 16 months versus those who were deceased before that age had undergone cardiovascular surgery at an older age (13 months, range 3-72, vs. 2 months, range 2-2, p = 0.03). Survival was better in those with single amino acid substitutions/small in-frame deletions than in those with large in-frame deletions (p = 0.007), but variants involving a cysteine substitution in an EGF-like domain versus those involving other amino acids did not significantly influence survival. EoMFS ranges from a (pre-)neonatal life-threatening disorder to a disorder with enhanced survival, creating a window for cardiovascular surgery. Individuals with single amino acid substitutions/small in-frame deletions had better survival compared to those with variants significantly impacting exon 24-32 length.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596236","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

From Function to Mechanism: Unveiling the Role of Small Nucleolar Ribonucleic Acids in Digestive Tumours.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-06 DOI: 10.1111/cge.14739

Dongxin Xi, Guli Shayila Dui Sanbai, Min Jiang, Zhihao Zhang, Taoran Sun, Weijia Wang, Yu Guo

{"title":"From Function to Mechanism: Unveiling the Role of Small Nucleolar Ribonucleic Acids in Digestive Tumours.","authors":"Dongxin Xi, Guli Shayila Dui Sanbai, Min Jiang, Zhihao Zhang, Taoran Sun, Weijia Wang, Yu Guo","doi":"10.1111/cge.14739","DOIUrl":"https://doi.org/10.1111/cge.14739","url":null,"abstract":"Small nucleolar ribonucleic acids (snoRNAs) have emerged as crucial regulators in various biological processes and have garnered significant attention for their potential roles in cancer. These noncoding ribonucleic acids (RNAs) primarily guide ribosomal RNA (rRNA) pseudouridylation and 2'-O-methylation modifications and exhibit stable expression in the serum, making them promising biomarkers and therapeutic targets. Digestive tract cancer poses a severe global health threat due to its high mortality rate and difficulty in early detection. Understanding the molecular mechanisms underlying tumor development is critical for improving diagnostic and therapeutic strategies. Small nucleolar RNAs, with their diverse functions and stable presence in biological fluids, offer a unique opportunity to address these challenges. Small nucleolar RNAs are a class of small noncoding RNAs mainly located in the nucleolus of eukaryotic cells. They play essential roles in the maturation and modification of rRNAs, transfer RNAs, and small nuclear RNAs. They also participate in alternative splicing regulation and exhibit microRNA-like functions, influencing various cellular processes. Abnormal expression of snoRNAs has been closely linked to the development, invasion, and metastasis of digestive system tumors. Given their stable expression in serum and the ability to function independently of host genes, snoRNAs hold great potential as biomarkers for early screening, prognosis prediction, and therapeutic targets in digestive system tumors. Their involvement in key signaling pathways and molecular mechanisms provides a foundation for developing targeted therapies and improving patient outcomes. This review highlights the significance of snoRNAs in digestive system tumors, their biological roles, connections to cancer progression, and potential clinical applications. Further exploration of snoRNAs is expected to provide new insights into the diagnosis and treatment of digestive system tumors.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572431","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

Impact of SDHA Mutations on Yeast Growth and Mitochondrial Function. Case Study Linking Genetic Findings to Clinical Phenotypes. SDHA 基因突变对酵母生长和线粒体功能的影响。将基因发现与临床表型联系起来的案例研究。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-06 DOI: 10.1111/cge.14738

Camilla Meossi, Alessandro De Falco, Marco Marchi, Anna Rubegni, Stefano Pagano, Rosanna Trovato, Claudia Nesti, Flavio Dal Canto, Emanuele Bartolini, Leonardo Salviati, Filippo Maria Santorelli

引用次数: 0

Limited Diagnostic Utility of PRDM10 Analysis in Birt-Hogg-Dubé Syndrome: Experience in 313 Consecutive Patients.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-03-03 DOI: 10.1111/cge.14737

Agathe Hercent, Ibrahima Ba, Dimitri Tchernitchko

引用次数: 0

NEUROMYODredger: Whole Exome Sequencing for the Diagnosis of Neurodevelopmental and Neuromuscular Disorders in Seven Countries.

IF 2.9 3区医学

Clinical Genetics Pub Date : 2025-02-25 DOI: 10.1111/cge.14736

Edoardo Malfatti, Alexandru Caramizaru, Hane Lee, JiHye Kim, Hussein Shoaito, Alessandra Pennisi, Sarah Souvannanorath, François-Jérôme Authier, Andreea Dumitrescu, Nagia Fahmy, Rosa Elena Escobar-Cedillo, Antonio Miranda-Duarte, Alexandra Berenice Luna-Angulo, Sonia Nouioua, Ouissem Benchaabi, Meriem Tazir, Sihem Hallal, Peggy Martinez, Claudia Castiglioni, Amelia Dobrescu, Homa Tajsharghi

{"title":"NEUROMYODredger: Whole Exome Sequencing for the Diagnosis of Neurodevelopmental and Neuromuscular Disorders in Seven Countries.","authors":"Edoardo Malfatti, Alexandru Caramizaru, Hane Lee, JiHye Kim, Hussein Shoaito, Alessandra Pennisi, Sarah Souvannanorath, François-Jérôme Authier, Andreea Dumitrescu, Nagia Fahmy, Rosa Elena Escobar-Cedillo, Antonio Miranda-Duarte, Alexandra Berenice Luna-Angulo, Sonia Nouioua, Ouissem Benchaabi, Meriem Tazir, Sihem Hallal, Peggy Martinez, Claudia Castiglioni, Amelia Dobrescu, Homa Tajsharghi","doi":"10.1111/cge.14736","DOIUrl":"https://doi.org/10.1111/cge.14736","url":null,"abstract":"Although substantial advancements have been made in genetic testing, several barriers continue to limit patient access, leading to delays in diagnosis, effective treatments, and preventative measures. The NEUROMYODredger-3billion Megaproject End the Diagnostic Odyssey grant offered free whole exome sequencing (WES) to 245 patients with undiagnosed neurodevelopmental or neuromuscular disorders in seven countries: Algeria, Chile, Egypt, France, Mexico, Peru, and Romania. We found pathogenic variants in 79 patients (diagnostic yield 32.24%)-36 neurodevelopmental (43.90%) and 43 neuromuscular (26.38%). Fifty patients harboured variants of uncertain significance (VUS, 20.40%)-14 neurodevelopmental (17.07%) and 36 neuromuscular (22.08%), and 116 patients had negative results (47.34%). NEUROMYODredger helped end the diagnostic odyssey in around 30% of patients, while ongoing functional studies and reanalysis strategies are used in order to reach more diagnoses. In conclusion, a singleton WES approach is valuable in determining the genetic diagnosis of neurodevelopmental and neuromuscular diseases, especially in low and middle-income countries.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499442","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