Clinical Genetics最新文献

Skeletal Phenotype in Mulibrey Nanism, A Monogenic Skeletal Dysplasia With Fibrous Dysplasia. Mulibrey Nanism（一种伴有纤维性发育不良的单基因骨骼发育不良）的骨骼表型。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-18 DOI: 10.1111/cge.14647

Susann Karlberg, Sanna Toiviainen-Salo, Marita Lipsanen-Nyman, Outi Mäkitie

{"title":"Skeletal Phenotype in Mulibrey Nanism, A Monogenic Skeletal Dysplasia With Fibrous Dysplasia.","authors":"Susann Karlberg, Sanna Toiviainen-Salo, Marita Lipsanen-Nyman, Outi Mäkitie","doi":"10.1111/cge.14647","DOIUrl":"10.1111/cge.14647","url":null,"abstract":"Mulibrey nanism (MUL) is a monogenic growth disorder caused by mutations in TRIM37, with pre-and postnatal growth failure, typical craniofacial features, perimyocardial heart disease, infertility and predisposition to tumors. Clinically, patients are gracile with relative macrocephaly, thin extremities, and narrow shoulders, but the full spectrum of skeletal features remains unknown. We conducted a cross-sectional study in order to further clarify the skeletal phenotype. We assessed radiographs of the long bones and spine in 33 MUL patients, aged 4.5-48 years (14 females and 19 males, median age 16.7 years) for skeletal features. Hospital records were reviewed for clinical characteristics and fractures. Results confirmed significant skeletal abnormalities related to MUL. Skeletal changes were present in all patients; long bones were slender and bowed with broad metaphyses and narrow diaphysis, the cortices were thick, and medullary cavities were narrow. The vertebral bodies were tall. Fibrous dysplasia was found in 19/33 patients (58%); changes were monostotic in 58% and polyostotic in 42%. Altogether 17/33 patients (52%) had a history of fractures. This study confirms that in addition to short stature, patients with MUL have a specific skeletal dysplasia. Our findings suggest an important role for TRIM37 in cellular functions governing skeletal modelling and remodelling.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667450","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

BRCC3-Associated Syndromic Moyamoya Angiopathy Diagnosed Through Clinical RNA Sequencing. 通过临床 RNA 测序确诊的 BRCC3 相关综合征莫亚莫亚血管病变。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-17 DOI: 10.1111/cge.14650

Myrrhe Venema, Fatimah Albuainain, Rachel Schot, Bob Roozenbeek, Frank Sleutels, Tjakko van Ham, Tahsin Stefan Barakat

{"title":"BRCC3-Associated Syndromic Moyamoya Angiopathy Diagnosed Through Clinical RNA Sequencing.","authors":"Myrrhe Venema, Fatimah Albuainain, Rachel Schot, Bob Roozenbeek, Frank Sleutels, Tjakko van Ham, Tahsin Stefan Barakat","doi":"10.1111/cge.14650","DOIUrl":"https://doi.org/10.1111/cge.14650","url":null,"abstract":"Moyamoya angiopathy is a cerebral vasculopathy causing progressive stenosis of the internal carotid arteries and the compensatory development of collateral blood vessels, leading to brain ischemia and an increased risk of cerebral haemorrhage. Although multiple non-genetic causes have been associated with moyamoya syndrome, it can also be associated with rare genetic syndromes. Moyamoya Disease 4, characterised by a short stature, hypergonadotropic hypogonadism and facial dysmorphism (MYMY4, OMIM #300845), also referred to as BRCC3-associated moyamoya syndrome, has so far been described in 11 individuals. Here, we describe a 23-year-old male presenting with moyamoya syndrome, global developmental delay and intellectual disability, epilepsy, short stature and dysmorphic features, who after > 17 years of uninformative diagnostics was diagnosed with BRCC3-associated moyamoya syndrome after clinical RNA-seq. Transcriptome analysis showed reduced expression of the likely disease-causing gene BRCC3 in patient-derived fibroblasts, which was subsequently found to be caused by a ~ 26 kb Xq28 deletion. We furthermore review all reported cases of BRCC3-associated moyamoya syndrome, further delineating this clinical entity.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645979","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, Clinical, and Biochemical Characterization of a Large Cohort of Palestinian Patients With Fanconi-Bickel Syndrome. 大量巴勒斯坦范柯尼-比克尔综合征患者的遗传、临床和生化特征。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-16 DOI: 10.1111/cge.14648

Tamer Hodrob, Alaaeddin Abusalameh, Ibrahim Ismail, Imad Dweikat, Sarah Abu Rmeilah, Mutaz Sultan, Bassam Abu Libdeh, Abd-Al-Salam Abu Libdeh, Shaher Shweiki, Nadirah Damseh

{"title":"Genetic, Clinical, and Biochemical Characterization of a Large Cohort of Palestinian Patients With Fanconi-Bickel Syndrome.","authors":"Tamer Hodrob, Alaaeddin Abusalameh, Ibrahim Ismail, Imad Dweikat, Sarah Abu Rmeilah, Mutaz Sultan, Bassam Abu Libdeh, Abd-Al-Salam Abu Libdeh, Shaher Shweiki, Nadirah Damseh","doi":"10.1111/cge.14648","DOIUrl":"https://doi.org/10.1111/cge.14648","url":null,"abstract":"This study aims to investigate the clinical, biochemical, and genetic characteristics of Fanconi-Bickel syndrome (FBS) in a cohort of 20 individuals from Palestine and to identify novel pathogenic variants. A retrospective analysis was conducted on medical records from Al-Makassed Hospital's pediatric department spanning 2015 to 2023. Individuals diagnosed with FBS via molecular genetic testing were included in the study. Among the 20 genetically confirmed FBS patients, hepatomegaly was prevalent in 95%, whereas 70% exhibited both developmental delay and hypophosphatemic rickets, and 68.4% experienced growth retardation. Hypertriglyceridemia (HTG) was universal. Elevated liver enzymes and alkaline phosphatase were common, along with hypophosphatemia (95%) and urinary abnormalities. Genetic analysis revealed five distinct SLC2A2 pathogenic variants, including three previously unreported variants: p.Gln23Arg (c.68A > G), p.Thr353Arg (c.1058_1059delinsGG), and an exon 7 deletion. This study presents the largest single-center cohort of FBS patients, expanding our understanding of the disorder's phenotypic and genotypic spectrum. Despite FBS generally carrying a favorable prognosis, timely diagnosis remains crucial to prevent severe complications.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643884","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

AMOTL1-Associated Multiple Congenital Anomalies (Craniofaciocardiohepatic Syndrome, CFCHS): A Novel Clinical Spectrum Including Craniofacial, Heart and Liver Abnormalities. AMOTL1相关多发性先天畸形（颅面心肝综合征，CFCHS）：包括颅面、心脏和肝脏异常的新临床谱系。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-13 DOI: 10.1111/cge.14644

Natalia Gallego-Zazo, Jair Tenorio-Castano, Alejandro Parra, Julián Nevado, Mario Cazalla, Elsa Lucas-Castro, Karen E Heath, María Palomares, Emma Soengas, M Dolores Lledín, Emily Larrea, Antonio Olveira, Beatriz Morte, Ángel Carracedo, Pablo Lapunzina

引用次数: 0

A Novel Compound Heterozygous Genotype of the WDR73 Gene Associated With a Psychomotor Retardation Syndrome Without Cerebellar Atrophy and Other CNS Structural Abnormalities. 一种新的 WDR73 基因复合杂合子基因型与精神运动发育迟缓综合征有关，但不伴有小脑萎缩和其他中枢神经系统结构异常。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-12 DOI: 10.1111/cge.14645

Enrique Nogueira, Beatriz Del Olmo, Lara Babín, Génesis Vizuete, Concepción Lobo, Cecilia González

引用次数: 0

Identification of a Rare Branch Point Variant in the SMS Gene in a Large Family With a Severe Form of Snyder-Robinson Syndrome. 在一个患有严重斯奈德-罗宾逊综合征的大家庭中发现 SMS 基因的罕见分支点变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-10 DOI: 10.1111/cge.14643

Antoine Civit, Nathalie Ronce, Benjamin Cogné, Thomas Besnard, David Laurenceau, Catherine Hubert, Marie-Pierre Moizard, Paul Gueguen, Annick Toutain, Marie-Laure Vuillaume

引用次数: 0

Genetic Analysis of Heterotaxy in a Consanguineous Cohort. 近亲群中异位症的遗传分析

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-08 DOI: 10.1111/cge.14641

Maarab Al-Korashy, Hadeel Binomar, Abeer Al-Mostafa, Ibrahim Al-Mogarri, Saud Al-Oufi, Mohamed Al-Admawi, Mansour Al-Jufan, Najmeddine Echahidi, Amal Mokeem, Ahmed Alfares, Khushnooda Ramzan, Sahar Tulbah, Aisha Al-Qahtani, Saud Takroni, Sateesh Maddirevula, Zuhair Al-Hassnan

{"title":"Genetic Analysis of Heterotaxy in a Consanguineous Cohort.","authors":"Maarab Al-Korashy, Hadeel Binomar, Abeer Al-Mostafa, Ibrahim Al-Mogarri, Saud Al-Oufi, Mohamed Al-Admawi, Mansour Al-Jufan, Najmeddine Echahidi, Amal Mokeem, Ahmed Alfares, Khushnooda Ramzan, Sahar Tulbah, Aisha Al-Qahtani, Saud Takroni, Sateesh Maddirevula, Zuhair Al-Hassnan","doi":"10.1111/cge.14641","DOIUrl":"https://doi.org/10.1111/cge.14641","url":null,"abstract":"Heterotaxy (HTX) is a group of clinical conditions with a shared pathology of dislocation of one or more organs along the left-right axis. The etiology of HTX is tremendously heterogeneous spanning environmental factors, chromosomal aberrations, mono/oligogenic variants, and complex inheritance. However, in the vast majority of cases, the etiology of HTX remains elusive. Here, we sought to describe the yield of genetic analysis and spectrum of variants in HTX in our highly consanguineous population. Twenty-four affected individuals, from 19 unrelated families, were consecutively recruited. Genetic analysis, with exome sequencing, genome sequencing, or multigene panel, detected 9 unique variants, 7 of which were novel, in 8 genes known to be implicated in autosomal recessive form of HTX (C1orf127, CCDC39, CIROP, DNAAF3, DNAH5, DNAH9, MMP21, and MNS1) providing a yield of 42.1%. Of note, 7 of the 9 variants were homozygous, while 2 were inherited in compound heterozygosity, including a heterozygous CNV deletion. A search for candidate genes in negative cases did not reveal a plausible variant. Our work demonstrates a relatively high yield of genetic testing in HTX in a consanguineous population with an enrichment of homozygous variants. The significant genetic heterogeneity observed herewith underscores the complex developmental mechanisms implicated in the pathogenesis of HTX and supports adopting a genome-wide analysis in the diagnostic evaluation of HTX.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603552","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 Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance. 罕见疾病中的过多携带者表明大多数意义不明的变异体具有非致病性效应。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-11-05 DOI: 10.1111/cge.14642

Stefano Medaglia, Jaume Reig-Palou, Ariadna Bellés, Nerea Moreno-Ruiz, Jairo Rodríguez, Xavier Armengol, Juan Ignacio Aróstegui, Lluís Armengol, Juan José Guillén, Hafid Laayouni, Ferran Casals

{"title":"The Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance.","authors":"Stefano Medaglia, Jaume Reig-Palou, Ariadna Bellés, Nerea Moreno-Ruiz, Jairo Rodríguez, Xavier Armengol, Juan Ignacio Aróstegui, Lluís Armengol, Juan José Guillén, Hafid Laayouni, Ferran Casals","doi":"10.1111/cge.14642","DOIUrl":"https://doi.org/10.1111/cge.14642","url":null,"abstract":"Functional annotation and interpretation of genetic variants are a critical step in genetic diagnosis, as it may lead to personalized therapeutic options and genetic counseling. While the number of confirmed pathogenic genetic variants in an individual is relatively low, the number of variants of uncertain significance (VOUS) can be considerably higher, increasing the number of potential carriers of genetic disorders. Thus, reducing uncertainty and assessing the real effect of VOUS are crucial for clinical and medical genetics. In this study, we evaluated the efficacy of genetic screening technologies in accurately predicting pathogenic variants and their corresponding disease prevalence in a cohort of over 6000 healthy individuals involved in assisted reproduction programs. Using data from 305 genes associated with recessive disorders, we determined the frequency of carriers of pathogenic variants and VOUS in our dataset and compared the predicted prevalence based on this information with reported population prevalence data. The higher predicted prevalence in some disorders when considering VOUS suggests a mostly benign effect.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582310","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

PERCC1-Related Congenital Enteropathy. 与 PERCC1 相关的先天性肠病

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-29 DOI: 10.1111/cge.14638

Lena S Kerle, Pia Karlsland Åkeson, Thomas Müller, Andreas R Janecke

引用次数: 0

Recognisable Neuroradiological Findings in Five Neurogenetic Disorders. 五种神经遗传性疾病中可识别的神经放射学发现。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-27 DOI: 10.1111/cge.14637

Jessica Rosenblum, Marije Meuwissen, Anna C Jansen, Renske Oegema, Nihaal Reddy, Kshitij Mankad, Sniya Sudhakar

{"title":"Recognisable Neuroradiological Findings in Five Neurogenetic Disorders.","authors":"Jessica Rosenblum, Marije Meuwissen, Anna C Jansen, Renske Oegema, Nihaal Reddy, Kshitij Mankad, Sniya Sudhakar","doi":"10.1111/cge.14637","DOIUrl":"https://doi.org/10.1111/cge.14637","url":null,"abstract":"The rate of discovery and increased understanding of genetic causes for neurodevelopmental disorders has peaked over the past decade. It is well recognised that some genes show marked variability in neuroradiological phenotypes, and inversely, some radiological phenotypes are associated with several different genetic conditions. However, some readily recognisable brain magnetic resonance imaging (MRI) patterns, especially in the context of corresponding associated clinical findings, should prompt consideration of a pathogenic variant in a specific gene or gene pathway. As these conditions can often prove challenging to diagnose, a clinical suspicion of a specific disorder may be invaluable to guide and interpret genetic testing. This review focuses on five neurogenetic syndromes with recognisable brain findings that radiologists, paediatric neurologists, geneticists, and other specialists involved in neurodevelopmental disorders should be able to recognise in order to pinpoint the gene or gene groups involved and delve into their molecular mechanisms. The comprehensively reviewed conditions include DDX3X-related neurodevelopmental disorder, Van Maldergem syndrome, NMDAR-related disorders, EML1-associated disorder and ARFGEF2-related periventricular nodular heterotopia with microcephaly.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496294","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