European journal of medical genetics最新文献

{"title":"Tachycardiomyopathy-like presentation in neonatal MCAD deficiency: A novel cardiac phenotype","authors":"Elisabetta Morana ,&nbsp;Federico Baronio ,&nbsp;Marcello Lanari ,&nbsp;Egidio Candela ,&nbsp;Rita Ortolano ,&nbsp;Simone Bonetti ,&nbsp;Gabriele Bronzetti ,&nbsp;Giacomo Biasucci ,&nbsp;Tammam Hasan ,&nbsp;Luca Ragni ,&nbsp;Andrea Donti","doi":"10.1016/j.ejmg.2026.105070","DOIUrl":"10.1016/j.ejmg.2026.105070","url":null,"abstract":"<div><h3>Background</h3><div>Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder in Europe. Clinical onset typically occurs between 3 and 24 months of life with hypoketotic hypoglycemia, while neonatal presentations are less common. Although the disorder classically manifests with metabolic decompensation, atypical cardiac involvement has occasionally been reported but remains exceedingly rare. MCADD is included in many newborn screening programs, enabling early detection and timely management.</div></div><div><h3>Case presentation</h3><div>We report a full-term female neonate who, at 3 days of life, developed severe metabolic decompensation with refractory supraventricular tachyarrhythmias, severe systolic dysfunction, and biventricular dilation requiring maximal inotropic support. Expanded newborn screening revealed a profile consistent with MCADD, and genetic testing identified a homozygous variant in the <em>ACADM</em> gene, described according to HGVS nomenclature as ACADM(NM_000016.6):c.985A &gt; C p.(Lys329Gln). Disease-specific management, including high-rate intravenous glucose administration, carnitine supplementation, and a tailored low-fat diet, resulted in complete normalization of cardiac function within 48 hours.</div></div><div><h3>Discussion</h3><div>This case represents a tachycardiomyopathy-like presentation of neonatal-onset MCADD, a novel and rarely described cardiac phenotype. It emphasizes the importance of considering fatty acid oxidation disorders in the differential diagnosis of unexplained arrhythmias and cardiomyopathy in neonates, particularly before newborn screening results are available.</div></div><div><h3>Conclusions</h3><div>Early diagnosis and prompt initiation of metabolic treatment are essential to reverse potentially life-threatening cardiac manifestations in MCADD. This report highlights a novel phenotype and expands the clinical spectrum of neonatal-onset MCADD.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"80 ","pages":"Article 105070"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrafamilial variability of myoclonic dystonia in a large French family carrying a novel SGCE variant","authors":"Cyprian Popescu","doi":"10.1016/j.ejmg.2026.105071","DOIUrl":"10.1016/j.ejmg.2026.105071","url":null,"abstract":"<div><div>Myoclonus–dystonia syndrome (MDS) is an autosomal dominant movement disorder most caused by pathogenic variants in SGCE, an imprinted gene subject to maternal silencing. While numerous pathogenic variants have been reported, the extent and determinants of intrafamilial variability remain incompletely understood. We investigated a large French family in which ten individuals across three generations presented with myoclonic jerks, dystonia, or combined phenotypes. Trio whole-exome sequencing performed in the proband, her affected brother, and her affected father identified a heterozygous SGCE variant, NM_003919.3:c.406T &gt; G, predicting a p.Cys136Gly substitution in a highly conserved cysteine-rich extracellular domain of ε-sarcoglycan. The variant segregated with disease in all clinically affected individuals for whom DNA was available and was absent from population databases. The phenotypic spectrum ranged from mild, stress-induced myoclonus in females to early-onset myoclonus with cervical dystonia and alcohol responsiveness in males, consistent with imprinting effects and sex-dependent modifiers. Variant interpretation using ACMG/AMP criteria (PM1, PM2, PM5, PP1-strong, PP2, PP3) supports a pathogenic classification. This previously unreported SGCE missense variant expands the mutational spectrum of MDS and further illustrates the substantial intrafamilial variability of SGCE-related disease.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"80 ","pages":"Article 105071"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel frameshift CUX2 variant in a patient with epilepsy and global developmental delay: Phenotypic and genotypic expansion","authors":"Ferruccio Romano ,&nbsp;Mohammad Sadegh Shams Nosrati ,&nbsp;Francesca Madia ,&nbsp;Marzia Ognibene ,&nbsp;Monica Traverso ,&nbsp;Marta Breda ,&nbsp;Alireza Dostmohammadi ,&nbsp;Marcello Scala ,&nbsp;Federico Zara ,&nbsp;Maria Margherita Mancardi ,&nbsp;Valeria Capra","doi":"10.1016/j.ejmg.2025.105064","DOIUrl":"10.1016/j.ejmg.2025.105064","url":null,"abstract":"<div><div>The Cut Like Homeobox 2 (<em>CUX2</em>) gene encodes a transcription factor critical for neuronal development. Monoallelic pathogenic <em>CUX2</em> variants are associated with developmental and epileptic encephalopathy 67 (DEE67), an autosomal dominant disorder characterized by variable clinical pictures including early-onset seizures, global developmental delay, and intellectual disability. While most variants described in the literature are missense, only one frameshift variant is reported as likely pathogenic for DEE67 in the ClinVar database. In this study, we report the patient, an 8-year-old girl with clinical features compatible with DEE67, who carries a novel <em>de novo</em> frameshift variant, c.633_636del p.(His211Glnfs∗3), in the <em>CUX2</em> gene. Although formally classified as a Variant of Uncertain Significance (VUS) based on stringent ACMG criteria, the variant is predicted to be a null allele, likely leading to <em>CUX2</em> haploinsufficiency via Nonsense-Mediated Decay (NMD). Clinically, her epileptic phenotype consisted of a single generalized tonic-clonic seizure, of milder entity and more treatment-responsive than those of other reported DEE67 cases. This report expands the genotypic spectrum of CUX2-related disorders and provides further evidence supporting haploinsufficiency as a pathogenic mechanism, while describing a milder clinical presentation that broadens the phenotypic spectrum of DEE67.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"79 ","pages":"Article 105064"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrence of occipital meningocele in 2 fetal sibs due to monoallelic MSX2 variant","authors":"Andreea-Catalina Fetecau ,&nbsp;Sarah Grotto ,&nbsp;Olivia Anselem ,&nbsp;Clémence Molac ,&nbsp;Jérémy Bertrand ,&nbsp;Laurence Lœuillet ,&nbsp;Tania Attie-Bitach","doi":"10.1016/j.ejmg.2025.105065","DOIUrl":"10.1016/j.ejmg.2025.105065","url":null,"abstract":"<div><div>Occipital encephaloceles are neural tube abnormalities characterized by a median defect of the occipital bone with herniation of brain structures usually contained in a membranous sac. Intracranial structures that protrude range from meninges (meningocele) to cerebral tissue such as occipital lobes, rarely cerebellum, brainstem or torcula.</div><div>We present two fetal sibs with occipital meningocele caused by a maternal <em>MSX2</em> variant identified by whole genome sequencing. Apart from the occipital meningocele, other cerebral abnormalities were found which led to the termination of the two pregnancies. The autopsy confirmed the prenatal findings. Upon clinical examination of the mother, a small scalp defect was discovered consistent with <em>MSX2</em> gene variant.</div><div>To our knowledge, only one case of occipital meningocele caused by <em>MSX2</em> gene haploinsufficiency has been reported, with maternal inheritance. This paper is aimed at confirming the link between <em>MSX2</em> gene variant and fetal occipital encephalocele, as well as its clinical variability.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"79 ","pages":"Article 105065"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Italian Angelman Syndrome Registry (IReAS): a tool for standardized data collection and genotype-phenotype analysis","authors":"Giorgia Buoncuore ,&nbsp;Marco Salvatore ,&nbsp;Adele Rocchetti ,&nbsp;Lorenzo Facciaroni ,&nbsp;Edvige Veneselli ,&nbsp;Maurizio Elia ,&nbsp;Silvia Russo ,&nbsp;Michelina Armando ,&nbsp;Michele Germano ,&nbsp;Tommaso Prisco ,&nbsp;Stefano Sartori ,&nbsp;Gemma Marinella ,&nbsp;Roberta Battini ,&nbsp;Giuseppe Gobbi ,&nbsp;Paola Torreri ,&nbsp;Angelman Syndrome Registry working group","doi":"10.1016/j.ejmg.2026.105067","DOIUrl":"10.1016/j.ejmg.2026.105067","url":null,"abstract":"<div><h3>Background</h3><div>Angelman syndrome (AS) is a rare and heterogeneous genetic disorder characterized by intellectual and psychomotor delay, speech deficits, seizures and behavioural issues. To evaluate the feasibility of collecting data by many Italian centers involved in pathology management, and to investigate the relationship between various symptoms and genotypes, a dedicated AS registry was developed.</div><div>This study aims to present preliminary findings from the Italian AS registry (IReAS), with a specific focus on exploring genotype-phenotype correlations.</div></div><div><h3>Materials and methods</h3><div>The IReAS, established in 2020, aims to collect information from 14 different Italian referral. It includes demography, diagnosis and genetic, patient status, therapeutic interventions and mortality data collection.</div></div><div><h3>Results</h3><div>213 patients (55.4 % female <em>vs</em> 44.6 % male) were included in the IReAS during the 2020–24 period. Average age at genetic diagnosis was 3.8 years; 63 % of patients was paediatric; 70.4 % of subjects had maternal deletion. Most patients exhibited global developmental delay (100 %), movement disorders (94.8 %), behavioral abnormalities (96.2 %), and a total lack of language development (95.8 %). Epilepsy is also highly prevalent (80.3 %), with a significantly higher incidence in patients with maternal deletion compared to non-deletion groups (88 % <em>vs</em> 61.9 %).</div></div><div><h3>Conclusions</h3><div>The IReAS provides comprehensive data on the diagnosis, genetic subtypes and clinical features of AS patients. It can facilitate genotype-phenotype correlation analyses, offering insights into the AS natural history and potential implications for research on targeted therapies.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"79 ","pages":"Article 105067"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic spectrum of variants in the FIG4 gene: variants associated with Charcot-Marie-Tooth 4J and parkinsonism","authors":"Barbora Lauerova ,&nbsp;Radim Mazanec ,&nbsp;Katja Eggerman ,&nbsp;Dana Safka Brozkova ,&nbsp;Annette Lischka ,&nbsp;Pavel Seeman ,&nbsp;Mikulas Mikula ,&nbsp;Petra Lassuthova","doi":"10.1016/j.ejmg.2025.105055","DOIUrl":"10.1016/j.ejmg.2025.105055","url":null,"abstract":"<div><div>Biallelic variants in the <em>FIG4</em> gene cause Charcot-Marie-Tooth type 4J (CMT4J) and Yunis-Varon syndrome. There is increasing evidence of phenotypic overlap between CMT4J and Yunis-Varon syndrome, which presents with peripheral neuropathy and central nervous system (CNS) abnormalities, particularly parkinsonism. We aim to extend and specify the phenotype-genotype correlation of the <em>FIG4</em> variants by presenting four cases of CMT4J, including two with parkinsonism. All patients carried the pathogenic <em>FIG4</em> variant c.122T &gt; C p.(Ile41Thr) in compound heterozygosity with another variant: c.793C &gt; T p.(Arg265∗), c.498-1G &gt; A, or c.447-2A &gt; C. Disease onset occurred in the first or second decade of life. All presented with demyelinating sensorimotor polyneuropathy, distal muscle weakness of the upper and lower limbs, and foot deformity. In one patient, the muscle weakness was asymmetrical. Two patients developed parkinsonism. Our findings expand the phenotypic spectrum of <em>FIG4</em>-related disorders, reinforcing the link between CMT4J and parkinsonism. These insights are crucial for improving genetic diagnosis and advancing potential therapeutic strategies.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105055"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative treatments of pediatric spinal muscular atrophy: The decision-making process in France","authors":"Maelle Biotteau ,&nbsp;Juliette Ropars ,&nbsp;Brigitte Chabrol ,&nbsp;Isabelle Desguerre ,&nbsp;Christine Barnéria ,&nbsp;Claude Cances","doi":"10.1016/j.ejmg.2025.105044","DOIUrl":"10.1016/j.ejmg.2025.105044","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is a devastating early-onset genetic disease characterized by motor neuron degeneration. For several years, an early access program has facilitated the use of three innovative therapies in France. To better define the therapeutic strategy following innovative therapy approval, an online expert committee within the French Rare Health Care for Neuromuscular Diseases Network (FILNEMUS) evaluates early diagnosed children and treatment-naive SMA cases during pediatric SMA multidisciplinary team meetings (<em>ps</em>MTMs). The decision process leading to molecule choice or palliative care encompasses pretreatment data collection, case presentation during <em>ps</em>MTMs, decision support, collective decision-making, and consensus, including the place assigned to parents. The process of setting up a nationwide online network of experts seems to be an effective, reactive and useful procedure in choosing the appropriate therapeutic option for newly diagnosed SMA children.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105044"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare features in Feingold syndrome type 1","authors":"Fanny Ferroul ,&nbsp;Sarah Snanoudj ,&nbsp;Gaëlle Leterme ,&nbsp;Kheira Mezouaghi ,&nbsp;Marie Kieffer-Traversier ,&nbsp;Tristan Celse ,&nbsp;Jessica Dospeux ,&nbsp;Thomas Huby ,&nbsp;Pauline Marzin ,&nbsp;Godelieve Morel ,&nbsp;Frédérique Payet ,&nbsp;Mathilde Remy ,&nbsp;Laetitia Sennsfelder ,&nbsp;Marta Spondenkiewicz ,&nbsp;Bérénice Roy-Doray ,&nbsp;Jeanne Amiel ,&nbsp;Veronique Pingault ,&nbsp;Jean-Luc Alessandri","doi":"10.1016/j.ejmg.2025.105049","DOIUrl":"10.1016/j.ejmg.2025.105049","url":null,"abstract":"<div><div>Feingold syndrome type 1 (FS1) (OMIM 164280) is an autosomal dominant condition due to heterozygous loss of function variants in <em>MYCN</em> gene or to 2p24 deletion encompassing <em>MYCN</em> gene. The core features of FS1 are digital anomalies, microcephaly, facial dysmorphism, short stature, esophageal/duodenal atresia, and mild learning disabilities. Additional features are reported in a minority of patients, such as cardiac and renal anomalies. Sensorineural deafness is reported in 7 % of the patients. Other features can be associated with classical features of FS1 in patients with 2p deletion including <em>MYCN</em> and other genes. Recently, absence of the flexor pollicis longus tendon has been reported as a new skeletal feature in a pedigree segregating a <em>MYCN</em> variant.</div><div>Here, we reported on three patients having FS1 without gastrointestinal atresia and unusual features: laryngeal cleft, congenital deafness, agenesis of the corpus callosum, and radio ulnar-synostosis (RUS). After the extension of the genetic screening, RUS was considered as an independent condition linked to <em>SMAD6</em> variant.</div><div>Diagnosis of FS1 can be challenging when there are unusual features without digestive malformations drawing attention. In this situation, the diagnostic approach may be based on major criteria of FS1: i) brachymesophalangy of the 2nd and 5th fingers, brachydactyly of fingers and toes with or without 2/3 and/or 4/5 toe syndactylies, ii) microcephaly, and iii) radiographs of the feet to look for amesophalangy of toes. Extension of the genetic screening is required to eliminate the possibility of two independent conditions.</div><div>In addition to the previous recommendations, we advocate for a set of recommendations for evaluation of FS1 patients following initial diagnosis: systematic search of deafness, verification of the flexion of the interphalangeal joints of the thumbs, laryngoscopy in case of stridor or swallowing disorders, and finally systematic cerebral MRI.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105049"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"French recommendations on multi-gene panel testing in renal cell carcinoma","authors":"Sophie Giraud ,&nbsp;Pascaline Berthet ,&nbsp;Caroline Abadie ,&nbsp;Nadine Andrieu ,&nbsp;Patrick R. Benusiglio ,&nbsp;Valérie Bonadona ,&nbsp;Olivier Caron ,&nbsp;Carole Corsini ,&nbsp;Isabelle Coupier ,&nbsp;Louise Crivelli ,&nbsp;Capucine Delnatte ,&nbsp;Pierre Devulder ,&nbsp;Antoine DE Pauw ,&nbsp;Sophie Dussart ,&nbsp;Anne-Paule Gimenez-Roqueplo ,&nbsp;Sophie Lejeune-Dumoulin ,&nbsp;Jessica Moretta ,&nbsp;Marie Muller ,&nbsp;Julie Tinat ,&nbsp;Stéphane Richard ,&nbsp;Nelly Burnichon","doi":"10.1016/j.ejmg.2025.105062","DOIUrl":"10.1016/j.ejmg.2025.105062","url":null,"abstract":"<div><h3>Introduction</h3><div>Renal cancers are inherited in about 5 % of cases and are associated with several genetic syndromes. Genetic testing is recommended for selected patients suspected of having hereditary syndromes. In the absence of guidelines regarding which genes should be included for carrying out genetic screening of these individuals, discrepancies existed among the next generation sequencing (NGS) multi-gene panels (MGP) used in French laboratories. There was therefore a clear need to standardise practices and offer patients with renal cancer a consensus-based genetic testing in France.</div></div><div><h3>Methods</h3><div>A working group comprising national experts from the French Genetic and Cancer Group Unicancer (GGC) and from the French network on Hereditary PREDIspositions to Renal Cancer (PREDIR) and encompassing medical geneticists, genetic counsellor, molecular biologists and epidemiologists was established. The objective was to define a list of clinically relevant genes that should be included in a “GGC-PREDIR” approved NGS MGP for patients with renal cancer.</div><div>A list of 32 genes of interest was compiled following an exhaustive and critical review of the literature. The inclusion or exclusion of each gene was determined based on available data regarding risk, prevalence and analyses published from large studies of patients.</div></div><div><h3>Results</h3><div>The French group of experts defined a list of 12 genes of clinical and genetic counselling relevance comprising <em>BAP1</em>, <em>FH</em>, <em>FLCN</em>, <em>MET</em>, <em>PTEN</em>, <em>SDHA</em>, <em>SDHB</em>, <em>SDHC</em>, <em>SDHD</em>, <em>TSC1</em>, <em>TSC2</em> and <em>VHL</em> to be included in the national recommended “renal cancer” NGS MGP. For each of these genes, recommendations for renal surveillance are proposed.</div></div><div><h3>Conclusion</h3><div>Unlike hereditary predisposition to breast or colon cancer, hereditary renal cancer predispositions are rare syndromes and risk estimates are lacking for most of them. Prospective studies are needed to improve our knowledge.</div><div>The GGC-PREDIR experts retained 12 genes for inclusion in the NGS MGP for renal cancer patients. However, the panel will be expanded on the basis of regularly updated data from the medical literature.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105062"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial hypertrophic cardiomyopathy associated with TBX1 variation","authors":"Jie Zhang ,&nbsp;Yafei Deng ,&nbsp;Yaxin Huang ,&nbsp;Daoheng Hu ,&nbsp;Haiyan Wu ,&nbsp;Tao Lv ,&nbsp;Weng Yang ,&nbsp;Lilan Wan ,&nbsp;Fang Liu ,&nbsp;Jilin Hu","doi":"10.1016/j.ejmg.2025.105054","DOIUrl":"10.1016/j.ejmg.2025.105054","url":null,"abstract":"<div><h3>Background</h3><div>Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease characterized by significant genetic heterogeneity. While the T-box transcription factor 1 (<em>TBX1</em>) gene is known to cause congenital cardiovascular defects, it has not been previously associated with HCM.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing (WES) was performed to identify causative gene mutations in a recently diagnosed Chinese family with HCM. The mutation was confirmed using Sanger sequencing, which was also employed to investigate familial co-segregation. A literature review was conducted to analyze previously reported <em>TBX1</em> mutations and their associated phenotypes.</div></div><div><h3>Results</h3><div>A novel heterozygous frameshift mutation, <em>TBX1</em> (NM_080647.1):c.3_27dup (p.Met10Alafs∗167), was identified in affected family members. Familial co-segregation analysis revealed that this mutation correlated with the HCM phenotype. To date, no previous studies have reported an association between <em>TBX1</em> mutations and HCM, suggesting that this may represent a novel <em>TBX1</em>-related phenotype.</div></div><div><h3>Conclusion</h3><div>This study identifies familial HCM as a new phenotype linked to <em>TBX1</em> gene mutations. These findings expand the mutation and phenotype spectrum of <em>TBX1</em> and emphasize the need for further research to understand the mechanisms by which the c.3_27dup (p.Met10Alafs∗167) mutation leads to HCM.</div></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"78 ","pages":"Article 105054"},"PeriodicalIF":1.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}