Clinical Genetics最新文献_第2页

Precision Medicine in Cardiomyopathy: Advances and Future Directions. 心肌病的精准医学：进展和未来方向。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-21 DOI: 10.1111/cge.70072

Mahvish Mehdi, Sushma Verma, Bashir Ahmad Mir, Shrikant Verma, Aliya Abbas Rizvi, Asma Imran Ansari, Mohammad Abbas, Farzana Mahdi

{"title":"Precision Medicine in Cardiomyopathy: Advances and Future Directions.","authors":"Mahvish Mehdi, Sushma Verma, Bashir Ahmad Mir, Shrikant Verma, Aliya Abbas Rizvi, Asma Imran Ansari, Mohammad Abbas, Farzana Mahdi","doi":"10.1111/cge.70072","DOIUrl":"https://doi.org/10.1111/cge.70072","url":null,"abstract":"This review explores how precision medicine is transforming the diagnosis, classification, and treatment of cardiomyopathies. It focuses on the integration of genetic profiling, biomarkers, and imaging to deliver more tailored and effective care. We review major cardiomyopathy subtypes: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular, with a focus on genetic drivers, including mitochondrial mutations. Pediatric forms are discussed in the context of syndromic and non-syndromic differences. We highlight the clinical value of combining biomarkers (molecular and serological) with imaging modalities, such as echocardiography, for better risk stratification, especially in predicting sudden cardiac death. The utility of animal models in translating genetic findings into disease understanding is also emphasized. Finally, we touch on innovations like genome editing, gene therapies, and pharmacogenomics for personalized treatment. Precision medicine offers a promising future for cardiomyopathy care. By targeting the underlying causes and tailoring treatment to each patient's genetic and molecular profile, we can achieve more accurate diagnoses, better risk prediction, and improved outcomes, bringing us closer to truly individualized cardiovascular care.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112097","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

Identification of PDIA6 Mutation in a Case of Autosomal Recessive Polycystic Kidney Disease: A Case Report and Review of Literature. 1例常染色体隐性多囊肾病PDIA6突变的鉴定：1例报告及文献复习。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-20 DOI: 10.1111/cge.70074

Reem H Al-Hadidi, Lina A Abu Sirhan

{"title":"Identification of PDIA6 Mutation in a Case of Autosomal Recessive Polycystic Kidney Disease: A Case Report and Review of Literature.","authors":"Reem H Al-Hadidi, Lina A Abu Sirhan","doi":"10.1111/cge.70074","DOIUrl":"https://doi.org/10.1111/cge.70074","url":null,"abstract":"Autosomal recessive polycystic kidney disease (ARPKD) is a rare but severe hereditary renal disorder characterized by bilaterally enlarged, cystic kidneys and varying degrees of hepatic fibrosis, often leading to early-onset kidney failure and significant morbidity. While most ARPKD cases are linked to mutations in the PKHD1 gene, recent advances in genomic sequencing have revealed that mutations in other genes, including PDIA6, may contribute to similar phenotypes. The PDIA6 gene encodes protein disulfide isomerase A6, which plays a critical role in protein folding within the endoplasmic reticulum (ER) and in the regulation of ER stress responses. Here, we report a rare and complex case of a full-term male neonate born to consanguineous Syrian refugee parents, who presented with a clinical constellation of features including polycystic kidney disease, severe oligohydramnios, pulmonary hypoplasia, microcephaly, rib thoracic dysplasia, and global developmental delay. Genetic analysis using whole-exome sequencing identified a homozygous two-base deletion in exon 5 of the PDIA6, resulting in a premature stop codon. Early diagnosis via genomic tools is essential for prognosis, management, and genetic counseling.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091256","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 and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders. 儿童糖尿病与脑发育障碍相关的单基因原因的临床和分子异质性。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-19 DOI: 10.1111/cge.70066

Gabriele Di Pasquale, Camilla Valsecchi, Giulia Marie Smylie, Vincenzo Salpietro, Gian Vincenzo Zuccotti, Maurizio Delvecchio, Chiara Mameli

{"title":"Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders.","authors":"Gabriele Di Pasquale, Camilla Valsecchi, Giulia Marie Smylie, Vincenzo Salpietro, Gian Vincenzo Zuccotti, Maurizio Delvecchio, Chiara Mameli","doi":"10.1111/cge.70066","DOIUrl":"https://doi.org/10.1111/cge.70066","url":null,"abstract":"Monogenic Diabetes Mellitus refers to heterogeneous forms of diabetes mellitus (DM) caused by a single gene pathogenic variant. Neurodevelopmental disorders (NDDs) are clinically and molecularly heterogeneous conditions characterized by an impairment of the nervous system development and/or function, with a wide clinical spectrum of variability. Over the last decade, Next Generation Sequencing (NGS) approaches have played a crucial role in the discovery of many monogenic causes underlying both NDDs and diabetes. In this systematic review, we aim to overview novel and emerging monogenic diseases presenting with pediatric diabetes and concomitant NDDs. The literature search was run in PubMed and Embase with a set of appropriate keywords. We examined 26 articles. Pathogenic variants have been classified according to the age of diabetes onset. In-depth analysis has been conducted for the selected papers, focusing on clinical description and molecular implications for a definite disease-causing gene. Interesting papers have revealed in recent years the occurrence of potential shared disease mechanisms underlying glucose and insulin metabolism and brain development and function. The broad clinical and molecular spectrum of DM-associated NDDs highlights the importance of a comprehensive and multidisciplinary management of these emerging clinical conditions and the increasingly crucial role of appropriate therapeutic approaches.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085250","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

Biallelic TMEM126B Variants as a Novel Cause of Kidney Failure-Implications for Mitochondrial Genetic Testing in Nephrology. 双等位基因TMEM126B变异是肾衰竭的一种新原因——肾脏病中线粒体基因检测的意义。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-19 DOI: 10.1111/cge.70073

Zachary T Sentell, Anthony C T Cheung, Felicia Russo, Chantal Bernard, Rita Suri, Andrey V Cybulsky, Daniela Buhas, Thomas M Kitzler

引用次数: 0

Reanalysis of Whole Genome Sequencing Resolves Genetically Undiagnosed Patients With "RNUopathies". 全基因组测序的再分析解决了遗传上未确诊的“RNUopathies”患者。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-18 DOI: 10.1111/cge.70069

Shiqi Fan, Shuanghao Yang, Xiaojing Nie, Zhihua Yu, Yan Jiang, Miao Sun, Weiyue Gu, Xue Zhang

{"title":"Reanalysis of Whole Genome Sequencing Resolves Genetically Undiagnosed Patients With \"RNUopathies\".","authors":"Shiqi Fan, Shuanghao Yang, Xiaojing Nie, Zhihua Yu, Yan Jiang, Miao Sun, Weiyue Gu, Xue Zhang","doi":"10.1111/cge.70069","DOIUrl":"https://doi.org/10.1111/cge.70069","url":null,"abstract":"Neurodevelopmental disorders (NDD) are a group of complex conditions characterized by marked phenotypic heterogeneity, primarily involving impairments in cognitive, emotional, and motor development. Approximately 40%-60% of patients with rare NDD remain genetically undiagnosed. Recently, RNU2-2 and RNU5B-1 have been identified as novel genes underlying the \"RNUopathies\" a syndromic NDD caused by variants in non-coding spliceosomal genes. In this study, we aimed to focus on RNU2-2 and RNU5B-1 by analyzing the whole-genome sequencing (WGS) data from 18326 Chinese individuals (including 2970 trios and 9416 samples without parental data), among whom 4900 had confirmed NDD phenotypes. Reanalysis of WGS data solved the previously undiagnosed cases of four patients with NDD carrying de novo variants in RNU genes, including three patients carrying the RNU2-2 variants (two cases with n.4G>A and one case with n.35A>G), and one case with an unreported RNU5B-1 variant (n.38C>T). In this study, detailed phenotypic elaboration and comparison with previous studies help clinicians in more effective diagnosis of NDD and underscore the importance of reanalyzing negative genetic data, which deepens our understanding of the \"RNUopathies.\"","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085239","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 Correlation in Children With Cystic Fibrosis From India: A Multicentric Study. 印度儿童囊性纤维化的基因型-表型相关性：一项多中心研究

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-18 DOI: 10.1111/cge.70063

Kana Ram Jat, Madhumita Roy Chowdhury, Nitin Dhochak, Rakesh Lodha, Sneha Varkki, Prawin Kumar, Jagdish Goyal, Javeed Iqbal Bhatt, S K Kabra

{"title":"Genotype-Phenotype Correlation in Children With Cystic Fibrosis From India: A Multicentric Study.","authors":"Kana Ram Jat, Madhumita Roy Chowdhury, Nitin Dhochak, Rakesh Lodha, Sneha Varkki, Prawin Kumar, Jagdish Goyal, Javeed Iqbal Bhatt, S K Kabra","doi":"10.1111/cge.70063","DOIUrl":"https://doi.org/10.1111/cge.70063","url":null,"abstract":"The study aimed to report genotype-phenotype correlation in children with cystic fibrosis. This prospective multicentric study was done at four centres. Variants were tested for two common variants, followed by exome sequencing using NGS. Patients with cystic fibrosis who have one or more pathogenic/likely pathogenic variants were included in this study. The study included 260 children. Boys were more common (70.6% vs. 55.3%), and consanguinity was more prevalent (31.7% vs. 14.2%) in patients with non-c.1520_1522del variants. The 3849+10kbC>T variant had less pancreatic insufficiency, a higher age at diagnosis, and lower sweat chloride values compared to the c.1520_1522del variant. The median (IQR) age at diagnosis was significantly lower [1.5 (0.5, 7) vs. 4 (1.1, 9.4 years)], and pancreatic insufficiency (80.4% vs. 66.4%) and consanguinity (44% vs. 7.1%) were significantly more frequent in patients with homozygous variants compared to compound heterozygous variants. There was no difference in the proportion of Pseudomonas or Staphylococcus colonisation, spirometry parameters or frequency of bronchiectasis amongst various genetic groups. To conclude, the proportion of boys and consanguinity was higher with non-c.1520_1522del variants. The 3849+10kbC>T variant exhibited some peculiar phenotypic features. The patients with homozygous variants were younger at diagnosis and had higher pancreatic insufficiency.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079659","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

Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication. 与遗传性15q13微重复相关的msl2相关脑室肥大的产前诊断

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-15 DOI: 10.1111/cge.70071

Omar Zgheib, Thomas Rio Frio, Jean-Marie Pellegrinelli, Stefania Gimelli, Caterina Marconi, Delphine Le Mercier, Monica Rebollo Polo, Céline Habre, Joël Fluss, Russia Ha-Vinh Leuchter, Marc Abramowicz, Rosalinda Giannini, Siv Fokstuen

{"title":"Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication.","authors":"Omar Zgheib, Thomas Rio Frio, Jean-Marie Pellegrinelli, Stefania Gimelli, Caterina Marconi, Delphine Le Mercier, Monica Rebollo Polo, Céline Habre, Joël Fluss, Russia Ha-Vinh Leuchter, Marc Abramowicz, Rosalinda Giannini, Siv Fokstuen","doi":"10.1111/cge.70071","DOIUrl":"https://doi.org/10.1111/cge.70071","url":null,"abstract":"The Male-Specific Lethal 2 Homolog (MSL2) gene was recently reported to be responsible for a novel, rather severe neurodevelopmental syndrome including brain abnormalities. We report the first prenatal case of an MSL2-related pathology caused by a de novo MSL2 splice variant (c.142+1G>T). RNA study on amniotic fluid cells showed an intronic inclusion and frameshift, consistent with loss-of-function intolerance. The fetus, who presented with bilateral moderate ventriculomegaly, also carried a paternally inherited 15q13 microduplication. Brain MRI at 2 and 4 months of age showed stable, mildly enlarged lateral ventricles. Clinical evaluation at 11 months revealed only a mild developmental delay. This case illustrates the challenges in predicting the postnatal outcome of recently characterized syndromes with limited documented cases, especially in association with a second independent genetic anomaly. Follow-up will be crucial to better define the developmental impact of this first reported MSL2 splice mutation in combination with the 15q13 microduplication, and characterization of more patients with MSL2 mutations will contribute to expanding the phenotypic spectrum.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069196","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

Whole Exome Sequencing Based Diagnostics in Complex Childhood Epilepsy Syndromes-A Cohort Study on Clinical Utility. 基于全外显子组测序的复杂儿童癫痫综合征诊断——临床应用的队列研究

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-15 DOI: 10.1111/cge.70061

Alfiya Fasaludeen, Manna Jose, U Aswathi, Moinak Banerjee, Soumya Sundaram, Ashalatha Radhakrishnan, Madhusoodanan Urulangodi, Dinesh Gupta, Sheela Nampoothiri, Ramshekhar N Menon

{"title":"Whole Exome Sequencing Based Diagnostics in Complex Childhood Epilepsy Syndromes-A Cohort Study on Clinical Utility.","authors":"Alfiya Fasaludeen, Manna Jose, U Aswathi, Moinak Banerjee, Soumya Sundaram, Ashalatha Radhakrishnan, Madhusoodanan Urulangodi, Dinesh Gupta, Sheela Nampoothiri, Ramshekhar N Menon","doi":"10.1111/cge.70061","DOIUrl":"https://doi.org/10.1111/cge.70061","url":null,"abstract":"Studies from the subcontinent on the utility of Whole Exome Sequencing (WES) in electro-clinical phenotypes of childhood-onset drug-resistant epilepsy (DRE) syndromes, particularly the developmental and epileptic encephalopathies (DEE), are rare in the literature. Patients with DRE phenotypes of presumed genetic etiology with an age of onset of epilepsy < 12 years, with/without developmental encephalopathy, were included in this study. Our study cohort (N = 175) included 158 trios, 6 duos, and 11 proband-only samples. Age at onset of seizures was ≤ 3 years in 76.6% and > 3 years in 23.4%, with developmental delay noted in 80.6% of the cohort. The overall yield of pathogenic/likely pathogenic variants in WES was 38.9% (68/175, 19 were novel); for trio-WES it was 41.1%. Predominantly de novo variants accounted for 45 out of 68 cases (66.2%), and the most frequent disease-causing variants were missense (74%). Younger age at onset of epilepsy, female gender and electroclinical diagnosis of Dravet syndrome were associated with a higher yield as opposed to focal epilepsies. Precision medicine was considered tenable in 25/68 (36.8%) cases. Our study reveals a significant yield of trio-WES for de novo variants in childhood-onset DRE/DEE. Female gender, early age at onset, and specific electro-clinical phenotypes have a higher likelihood of identifying a monogenic etiology.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069256","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

Novel Variants in MDC1 Were Associated With Severe Oligoasthenoteratozoospermia. MDC1基因的新变异与严重少弱异性精子症相关。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-15 DOI: 10.1111/cge.70058

Xu Liu, Yu Wang, Chen Tan, Hujia Tan, Wenjun Wang, Pengcheng Hu, Yunxia Cao, Fengsong Wang, Yichang Lu, Fuxi Zhu

引用次数: 0

Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran. 外显子组测序揭示了遗传性骨骼疾病的新变异：来自伊朗西南部队列的见解。

IF 2.3 3区医学

Clinical Genetics Pub Date : 2025-09-15 DOI: 10.1111/cge.70070

Rezvan Zabihi, Mina Zamani, Niloofar Chamanrou, Jawaher Zeighami, Tahere Seifi, Saeed Ashoori, Sahere Parvas, Tahere Yadegari, Fateme Mousavi, Elham Khajevandian, Moslem Sarvari, Kobra Shojaei, Pardis Nourbakhsh, Bijan Keikhaei, Majid Aminzadeh, Raha Ahmadi, Marzieh Mohammadi Anaei, Alireza Sedaghat, Alihossein Saberi, Mohammad Hamid, Golamreza Shariati, Hamid Galehdari

{"title":"Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran.","authors":"Rezvan Zabihi, Mina Zamani, Niloofar Chamanrou, Jawaher Zeighami, Tahere Seifi, Saeed Ashoori, Sahere Parvas, Tahere Yadegari, Fateme Mousavi, Elham Khajevandian, Moslem Sarvari, Kobra Shojaei, Pardis Nourbakhsh, Bijan Keikhaei, Majid Aminzadeh, Raha Ahmadi, Marzieh Mohammadi Anaei, Alireza Sedaghat, Alihossein Saberi, Mohammad Hamid, Golamreza Shariati, Hamid Galehdari","doi":"10.1111/cge.70070","DOIUrl":"https://doi.org/10.1111/cge.70070","url":null,"abstract":"Genetic skeletal disorders (GSDs) comprise a diverse group of disorders that affect bone development and homeostasis. In some areas of Iran, GSD occurs more frequently than in other places for still unknown reasons. The aim of this study was to characterize the genetic landscape of GSDs in a cohort from southwestern Iran using Exome sequencing (ES), with a focus on identifying pathogenic and likely pathogenic variants. Osteogenesis Imperfecta (OI) was the most prevalent disorder, with an unexpectedly high frequency of autosomal recessive subtypes, likely due to a high consanguinity rate (61.3%) in the cohort. Achondroplasia (ACH) was the second most common disease and, comparable to another population, the NM_000142.5:c.1138G>A, p.(Gly380Arg), was the most common variant in FGFR3. ES identified twenty novel and fifteen previously reported pathogenic variants in several genes associated with GSDs. We provide the first comprehensive ES-based molecular diagnosis of GSDs in an Iranian population and uncover novel pathogenic variants that expand the known spectrum of variants. The results underscore the importance of genetic testing in the diagnosis of rare skeletal diseases and highlight the need for targeted genetic counseling in populations with high consanguinity.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063476","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