Clinical Genetics最新文献

Cerebral Ventriculomegaly With Abnormality of the Aqueduct of Sylvius: A Case Series. 脑室肿大伴脑脊液导水管异常一例。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-20 DOI: 10.1111/cge.70265

Romain Nicolle, Laurence Loeuillet, Bettina Bessieres, Lucile Boutaud, Sarah Grotto, Nicolas Bourgon, Maryse Bonniere, Jelena Martinovic, Aude Tessier, Nathalie Roux, Giulia Petrilli, Naima Talhi, Marion Lesieur-Sebellin, Jérémy Bertrand, Anaïs L'haridon, Aurélie Coussement, Marie-Laure Maurin, Marie-Paule Beaujard, Valérie Malan, Férechté Razavi, Tania Attie-Bitach

{"title":"Cerebral Ventriculomegaly With Abnormality of the Aqueduct of Sylvius: A Case Series.","authors":"Romain Nicolle, Laurence Loeuillet, Bettina Bessieres, Lucile Boutaud, Sarah Grotto, Nicolas Bourgon, Maryse Bonniere, Jelena Martinovic, Aude Tessier, Nathalie Roux, Giulia Petrilli, Naima Talhi, Marion Lesieur-Sebellin, Jérémy Bertrand, Anaïs L'haridon, Aurélie Coussement, Marie-Laure Maurin, Marie-Paule Beaujard, Valérie Malan, Férechté Razavi, Tania Attie-Bitach","doi":"10.1111/cge.70265","DOIUrl":"https://doi.org/10.1111/cge.70265","url":null,"abstract":"Fetal cerebral ventriculomegalies are brain anomalies with potentially poor neurodevelopmental prognosis. They are amenable to prenatal imaging, isolated or associated with other cerebral and/or extra-cerebral abnormalities. Most are obstructive due to a focal or diffuse dysgenesis of the ventricular system, disturbing the cerebro-spinal fluid outflow. Triventricular dilatation is the most common, predicting a lesion at the level of the aqueduct of Sylvius (AS). Although variants in several genes have recently been linked to ventriculomegaly, their role remains unclear, compromising our ability to predict the impact of such variations when detected prenatally. To go further, we report here a monocentric cohort of 51 fetuses with cerebral ventriculomegaly linked to dysgenetic AS and discuss phenotype/genotype correlations after neuropathological study. A genetic cause has been identified in 15 cases (29.4%) using different genetic methods available between 1992 and 2021: standard karyotyping, targeted mutation screening (Sanger sequencing), and Next Generation Sequencing. Dysgeneses of the AS are still controversial in their nosology and etiology; most are discussed on the basis of brain imaging findings alone. In this series, complete fetal and neuropathological examination allowed detection of key clinical and histopathological clues, allowing the orientation of molecular screenings and the identification of cellular mechanisms involved in triventricular dilatations.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227428","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

A Familial Case of Thauvin-Robinet-Faivre Syndrome (TROFAS), Presenting With Postaxial Polydactyly and Upper Lip Vascular Malformation. 家族性Thauvin-Robinet-Faivre综合征（TROFAS） 1例，表现为轴后多指畸形和上唇血管畸形。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-18 DOI: 10.1111/cge.70264

Federica Ruscitti, Xenia Latypova, Faustine Ageorges, Antonio Vitobello, Christophe Philippe, Frédéric Tran Mau Them, Yannis Duffourd, Georges Gelwane, Cherine Benzouid, Yline Capri

{"title":"A Familial Case of Thauvin-Robinet-Faivre Syndrome (TROFAS), Presenting With Postaxial Polydactyly and Upper Lip Vascular Malformation.","authors":"Federica Ruscitti, Xenia Latypova, Faustine Ageorges, Antonio Vitobello, Christophe Philippe, Frédéric Tran Mau Them, Yannis Duffourd, Georges Gelwane, Cherine Benzouid, Yline Capri","doi":"10.1111/cge.70264","DOIUrl":"https://doi.org/10.1111/cge.70264","url":null,"abstract":"Thauvin-Robinet-Faivre syndrome (TROFAS, OMIM #617107) is a recently identified autosomal recessive disorder characterised by syndromic overgrowth, facial dysmorphism, mild intellectual disability, variable congenital anomalies, and occasional tumour occurrence. TROFAS results from homozygous or compound heterozygous variants in the FIBP gene, encoding the intracellular binding protein for acidic fibroblast growth factor. This protein plays a role in the fibroblast growth factor (FGF) signalling pathway, which is involved in cell proliferation and contributes to the development of several structures, such as the nervous system, optic vesicles, and blood vessels. Prior to the present report, TROFAS has been described in 10 patients from seven families, four of which are of Turkish origin. We report two additional Turkish siblings from a previously unreported family harbouring the recurrent homozygous c.412-3_415dupCAGTTTG likely pathogenic variant in FIBP. Both presented with typical TROFAS features; however, the male sibling exhibited a more severe neurodevelopmental profile and additional malformations, including postaxial polydactyly and upper lip vascular malformation, which, to our knowledge, have not previously been reported in association with TROFAS. A detailed clinical characterisation of these two new cases contributes to a more comprehensive delineation of the syndrome, adding potentially novel phenotypic features requiring confirmation in additional patients.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220016","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

Expanding Clinical and Variant Spectrum of CBX1-Related Syndrome: Report of Three Novel Cases. 扩大cbx1相关综合征的临床和变异谱：三例新病例报告

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-13 DOI: 10.1111/cge.70262

Graciela Carrillo, Shuhei Fujino, Harrison Higgs, Anita Kabahizi, Randy Le, Rachel Rabin, John Pappas, Amy Crunk, Kara Ranguin, Jérémie Mortreux, Marilyn Lackmy, Carlos A Gadia, Matthew Hoi Kin Chau, Jill A Rosenfeld, Xi Luo, Kosuke Izumi

{"title":"Expanding Clinical and Variant Spectrum of CBX1-Related Syndrome: Report of Three Novel Cases.","authors":"Graciela Carrillo, Shuhei Fujino, Harrison Higgs, Anita Kabahizi, Randy Le, Rachel Rabin, John Pappas, Amy Crunk, Kara Ranguin, Jérémie Mortreux, Marilyn Lackmy, Carlos A Gadia, Matthew Hoi Kin Chau, Jill A Rosenfeld, Xi Luo, Kosuke Izumi","doi":"10.1111/cge.70262","DOIUrl":"10.1111/cge.70262","url":null,"abstract":"CBX1-related syndrome is characterized by developmental delay, hypotonia, autistic features, and mild dysmorphic features. This syndrome is caused by heterozygous missense variants in CBX1, which encodes heterochromatin protein 1 beta (HP1β). These variants are situated within the chromodomain of HP1β, a critical region that mediates the interaction between HP1β and trimethylated H3K9. While a prior study identified three individuals with pathogenic CBX1 variants, the variant and clinical spectrum of CBX1-related syndrome remain largely unknown. Here we report three patients with novel de novo heterozygous variants in CBX1. Patients with CBX1 p.(Leu40Pro) and p.(Cys60Arg) manifested with global developmental delay, while the patient with CBX1 p.(Cys60Gly) primarily exhibited speech delay without concurrent motor developmental delay. All variants reside within the chromodomain of the HP1β protein. Interestingly, in vitro cellular assays revealed that the CBX1 p.(Cys60Gly) variant showed an intermediate cellular phenotype between the wild type and the CBX1 p.(Leu40Pro) and p.(Cys60Arg) variants, suggesting a possible genotype-phenotype correlation. This report provides further evidence that missense variants within the chromodomain of HP1β cause a syndromic neurodevelopmental disorder, CBX1-related syndrome.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Homozygous ALCAM-CBLB Deletion at 3q13.11-q13.12 Defines a Candidate Novel Oculo-Skeletal-Immune Contiguous Gene Deletion Syndrome. 3q13.11-q13.12位点的ALCAM-CBLB纯合子缺失定义了一种候选的新型眼-骨-免疫连续基因缺失综合征

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-08 DOI: 10.1111/cge.70259

Nilay Kan Menkü, Mehlika Meryem Sarı, Filiz Başak Ergin, Tuğçe İnal, Kazım Seçgen, Avniye Kübra Baskın, Rüştü Fikret Akata, Fatih Ezgü

{"title":"A Homozygous ALCAM-CBLB Deletion at 3q13.11-q13.12 Defines a Candidate Novel Oculo-Skeletal-Immune Contiguous Gene Deletion Syndrome.","authors":"Nilay Kan Menkü, Mehlika Meryem Sarı, Filiz Başak Ergin, Tuğçe İnal, Kazım Seçgen, Avniye Kübra Baskın, Rüştü Fikret Akata, Fatih Ezgü","doi":"10.1111/cge.70259","DOIUrl":"https://doi.org/10.1111/cge.70259","url":null,"abstract":"To our knowledge, we report the first combined homozygous deletion of ALCAM and CBLB at 3q13.11-q13.12. The patient, a 14-year-old boy born to consanguineous parents, had a multisystem phenotype with severe congenital ocular and craniofacial anomalies, early-onset osteoporosis, progressive scoliosis, growth failure, congenital heart defect, humoral immunodeficiency, and chronic inflammatory findings. SNP array identified a 2.5-Mb homozygous deletion spanning ALCAM and CBLB, and expression studies confirmed complete absence of ALCAM and CBLB expression. Whole-exome sequencing did not identify an alternative molecular diagnosis. The clinical presentation is likely attributable to combined ALCAM and CBLB loss. Previous animal-model studies support interpretation of the individual phenotypic components by linking loss of these genes to craniofacial developmental abnormalities, skeletal findings, and immune dysregulation. We propose that this deletion may represent a candidate novel contiguous gene deletion syndrome. This case is the first human phenotype associated with complete ALCAM loss in a contiguous deletion and expands the clinical spectrum associated with disruption of ALCAM and CBLB.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135071","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

Analysis of Genomic Testing of Congenital Heart Disease in a Cohort From a Consanguineous Population. 同源人群先天性心脏病的基因组检测分析

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-08 DOI: 10.1111/cge.70250

Abeer Almostafa, Maarab Al-Korashy, Zarghuna Shinwari, Saud Takroni, Sahar Tulbah, Nadiah Al-Ruwaili, Aisha Alqahtani, Faten AlHadheq, Hadeel Binomar, Amal AlDowaihi, Hamzah Naji, Waleed Manea, Abdullah Alwadai, Dimpna C Albert Brotons, Abdulaziz Alfadley, Abdullah AlQwaee, Amani Othman, Abdullah Alhuzaimi, Saud Aloufi, Ghassan Siblini, Fadel Alfadley, Abdullah Alsehly, Mohammed Alhabdan, Ali Alakhfash, Mansour Aljoufan, Abdulrahman Almesned, Zohair Alhalees, Zuhair Al-Hassnan

{"title":"Analysis of Genomic Testing of Congenital Heart Disease in a Cohort From a Consanguineous Population.","authors":"Abeer Almostafa, Maarab Al-Korashy, Zarghuna Shinwari, Saud Takroni, Sahar Tulbah, Nadiah Al-Ruwaili, Aisha Alqahtani, Faten AlHadheq, Hadeel Binomar, Amal AlDowaihi, Hamzah Naji, Waleed Manea, Abdullah Alwadai, Dimpna C Albert Brotons, Abdulaziz Alfadley, Abdullah AlQwaee, Amani Othman, Abdullah Alhuzaimi, Saud Aloufi, Ghassan Siblini, Fadel Alfadley, Abdullah Alsehly, Mohammed Alhabdan, Ali Alakhfash, Mansour Aljoufan, Abdulrahman Almesned, Zohair Alhalees, Zuhair Al-Hassnan","doi":"10.1111/cge.70250","DOIUrl":"https://doi.org/10.1111/cge.70250","url":null,"abstract":"Congenital heart disease (CHD) is the most common type of birth defect with tremendous genetic heterogeneity. The aim of our study was to unravel the molecular pathology and the magnitude of recessive genotypes (RGs) in a cohort of CHD from our consanguineous population. In probands with CHD who were consecutively recruited, genetic analysis was conducted based on the most likely etiology to either copy number variants (CNVs) analysis, multigene panel, whole exome sequencing (WES), or whole genome sequencing (WGS). A total of 201 families were recruited, of whom 59.7% were consanguineous. The overall diagnostic yield of genetic testing was 34.8%, with significantly higher yield in syndromic compared to isolated CHD (48.8% vs. 11.8%, respectively, ***p < 0.0001). Pathogenic CNV were identified in 12.4% and single-nucleotides variants in 22.4%, with biallelic variants in only 6.5% of probands. In negative cases, analysis of WES/WGS data did not reveal plausible variants. The tremendous genetic heterogeneity with a minority of homozygous variants in our cohort suggests that RG may be considered a rare cause of CHD even in consanguineous population. Our findings support the integration of next-generation sequencing into routine clinical care of CHD and provide relevant ingredients for genetic counseling in consanguineous population.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135240","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

Two Truncating MITF Variants Expand the Phenotypic Spectrum of COMMAD Syndrome. 两个截断的MITF变异扩展了COMMAD综合征的表型谱。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-07 DOI: 10.1111/cge.70260

Andreas Pampanos, Anastasia-E Kostantinidou, Maria Tzetis, Vassilis Papanikolaou, Vasiliki Falaina, Aspasia Tsezou

{"title":"Two Truncating MITF Variants Expand the Phenotypic Spectrum of COMMAD Syndrome.","authors":"Andreas Pampanos, Anastasia-E Kostantinidou, Maria Tzetis, Vassilis Papanikolaou, Vasiliki Falaina, Aspasia Tsezou","doi":"10.1111/cge.70260","DOIUrl":"https://doi.org/10.1111/cge.70260","url":null,"abstract":"Pathogenic variants in MITF (Microphthalmia Transcription Factor) gene are associated with a spectrum of disorders, including Waardenburg syndrome type II and Tietz syndrome. Rare reports suggest that biallelic loss-of-function variants may result in a severe multisystem phenotype. We report an infant presenting with a phenotype consistent with COMMAD-like syndrome (Coloboma, Οsteopetrosis, Μicrophthalmia, Μacrocephaly, Αlbinism, and Deafness) who died in the early neonatal period. In addition to the core COMMAD features, the proband exhibited ectopic ossification, cardiac fibrosis and fibroelastosis, interstitial lung disease, ectopic renal tissue, liver steatosis, and hemosiderosis. Whole-exome sequencing identified two heterozygous truncating MITF variants, the previously reported c.961C>T (p.Arg321Ter) and a novel c.1135A>T (p.Lys379Ter) variant, both predicted to result in impaired MITF function. Parental testing was declined, precluding determination of the phase of the variants. To date, only one study has reported an association between biallelic MITF disruption and a severe clinical phenotype. Our findings provide additional evidence for this genotype-phenotype relationship and further expand the clinical spectrum of COMMAD syndrome. The present case further supports a role for impaired MITF function in the pathogenesis of a severe multisystem phenotype.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126883","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

Compound-Heterozygous PLVAP Missense Variants Associated With Attenuated Protein-Losing Enteropathy (DIAR10). 复合杂合PLVAP错义变异体与减毒蛋白丢失性肠病（DIAR10）相关。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-07 DOI: 10.1111/cge.70258

Jana Zídková, Dagmar Procházková, Petra Konečná, Kamila Réblová, Tereza Kramářová, Johana Kopčilová, Magdaléna Soukup Vodičková, Romana Borská, Lenka Fajkusová

引用次数: 0

A Novel ACAN Missense Variant in the G1 Domain Causes Short Stature, Advanced Bone Age, and Osteochondritis Dissecans: A Case Report and Literature Review. 一种新的G1结构域的ACAN错义变异导致身材矮小、骨龄提前和夹层性骨软骨炎：一例报告和文献回顾。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-02 DOI: 10.1111/cge.70241

Cuilan Lin, Dongxue Pan, Xin Lai, Simao Fu

引用次数: 0

Uncovering the Genetic Landscape of Pediatric Hearing Loss Along the Texas–Mexico Border 揭示沿德克萨斯-墨西哥边境儿童听力损失的遗传景观。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-01 Epub Date: 2026-08-26 DOI: 10.1111/cge.70224

Desiree Lanehart, Michelle Gray, Roberta Sierra, Camille Maldonado, Daniel Brooks, Hongzheng Dai, Aaly Rahimtoola, Sandy Magallan, Sarah Rodriguez, Jose Gamez, Pattie Rosenlund, Surya N. Mulukutla, Alberto Allegre, Lori Berry, Brendan Lee, Daryl A. Scott, Blake Vuocolo, Seema R. Lalani

{"title":"Uncovering the Genetic Landscape of Pediatric Hearing Loss Along the Texas–Mexico Border","authors":"Desiree Lanehart, Michelle Gray, Roberta Sierra, Camille Maldonado, Daniel Brooks, Hongzheng Dai, Aaly Rahimtoola, Sandy Magallan, Sarah Rodriguez, Jose Gamez, Pattie Rosenlund, Surya N. Mulukutla, Alberto Allegre, Lori Berry, Brendan Lee, Daryl A. Scott, Blake Vuocolo, Seema R. Lalani","doi":"10.1111/cge.70224","DOIUrl":"10.1111/cge.70224","url":null,"abstract":"Children in Health Professional Shortage Areas (HPSAs), including the US border regions, experience delays in the diagnosis of hereditary hearing loss (HL), driven primarily by limited access to specialized genetic services. Although approximately 60% of congenital HL has a genetic etiology, many affected children in these communities remain undiagnosed, delaying timely intervention. Project GIVE is an NIH-funded virtual genomics program that expands access to genome sequencing (GS) for children with undiagnosed multisystemic conditions along the Texas–Mexico border in the Rio Grande Valley (RGV) and El Paso regions of Texas, USA. Children (0–18 years) with suspected rare diseases were referred by regional healthcare professionals through a virtual portal, Consultagene, and underwent comprehensive virtual clinical genetics evaluation and trio GS. Among 23 Hispanic/Latino children evaluated for HL, 16 (~70%) received a molecular diagnosis. Of these, 56% had changes to medical management. Our findings demonstrate that high diagnostic yield for pediatric HL can be achieved in under-resourced populations when genomic testing barriers are addressed. As targeted therapies for hereditary HL emerge, broader implementation of comprehensive genetic testing in HPSAs is crucial to ensure timely medical interventions.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":"110 5","pages":"627-636"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cge.70224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The First Case of Isolated Uterine Atony as the Only Symptom in an Individual With ACTG2-Associated Visceral Myopathy 孤立性子宫张力作为actg2相关内脏肌病个体的唯一症状的第一例。

IF 2.1 3区医学

Clinical Genetics Pub Date : 2026-10-01 Epub Date: 2026-08-20 DOI: 10.1111/cge.70234

Brady A. Slater, Emily Muth, Naomi J. L. Meeks

引用次数: 0