Clinical Genetics最新文献_第2页

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

Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan. 日本支持原发性睫状肌运动障碍诊断的基因变异。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-27 DOI: 10.1111/cge.14640

Minako Hijikata, Kozo Morimoto, Masashi Ito, Keiko Wakabayashi, Akiko Miyabayashi, Hiroyuki Yamada, Naoto Keicho

{"title":"Genetic Variants Supporting the Diagnosis of Primary Ciliary Dyskinesia in Japan.","authors":"Minako Hijikata, Kozo Morimoto, Masashi Ito, Keiko Wakabayashi, Akiko Miyabayashi, Hiroyuki Yamada, Naoto Keicho","doi":"10.1111/cge.14640","DOIUrl":"https://doi.org/10.1111/cge.14640","url":null,"abstract":"Primary ciliary dyskinesia (PCD; OMIM 244400) is a rare genetic disorder affecting motile cilia and is characterized by impaired mucociliary clearance in the airway epithelium that leads to chronic oto-sinopulmonary manifestations. To date, over 50 PCD-causing genes have been identified, with these genes and their variants varying globally across populations. We performed targeted resequencing of 42 PCD-causative genes in 150 Japanese patients suspected of having PCD and identified pathogenic or likely pathogenic variants in 51 patients. Among these, 24 patients exhibited a homozygous deletion of DRC1 exons 1-4, the most common cause of PCD in Japan. The allele frequency of this deletion was estimated at 0.0034 (95% CI: 0.0025-0.0044), based on bioinformatic analysis of 7906 whole-genome sequences from the general Japanese population. Additionally, RNA sequencing of nasal samples supplemented in silico variant predictions, aiding in the identification of causative variants. Considering potential ethnic differences, it is essential to accumulate global data on these variants and their functional impacts.","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":"142496292","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 Two Novel Missense Variants in BNC1 in Han Chinese Patients With Non-syndromic Premature Ovarian Insufficiency. 在非综合征性卵巢早衰的中国汉族患者中发现 BNC1 的两个新型错义变异基因

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-27 DOI: 10.1111/cge.14639

Yuncheng Pan, Jitong Mo, Shuting Ren, Yifei Zhang, Feng Zhang, Xiaojin Zhang, Yanhua Wu

引用次数: 0

Utility of Optical Genome Mapping in Repeat Disorders. 光学基因组图谱在重复性疾病中的应用。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-22 DOI: 10.1111/cge.14633

Mehmet Burak Mutlu, Taner Karakaya, Hamide Betül Gerik Çelebi, Fahrettin Duymuş, Serhat Seyhan, Sanem Yılmaz, Uluç Yiş, Tahir Atik, Mehmet Fatih Yetkin, Hakan Gümüş

{"title":"Utility of Optical Genome Mapping in Repeat Disorders.","authors":"Mehmet Burak Mutlu, Taner Karakaya, Hamide Betül Gerik Çelebi, Fahrettin Duymuş, Serhat Seyhan, Sanem Yılmaz, Uluç Yiş, Tahir Atik, Mehmet Fatih Yetkin, Hakan Gümüş","doi":"10.1111/cge.14633","DOIUrl":"10.1111/cge.14633","url":null,"abstract":"Genomic repeat sequences are patterns of nucleic acids that exist in multiple copies throughout the genome. More than 60 Mendelian disorders are caused by the expansion or contraction of these repeats. Various specific methods for determining tandem repeat variations have been developed. However, these methods are highly specific to the genomic region being studied and sometimes require specialized tools. In this study, we have investigated the use of Optical Genome Mapping (OGM) as a diagnostic tool for detecting repeat disorders. We evaluated 19 patients with a prediagnosis of repeat disorders and explained the molecular etiology of 9 of them with OGM (5 patients with Facioscapulohumeral Muscular Dystrophy (FSHD), 2 patients with Friedreich's Ataxia (FA), 1 patient with Fragile X Syndrome (FXS), and 1 patient with Progressive Myoclonic Epilepsy 1A (EPM1A)). We confirmed OGM results with more widely used fragment analysis techniques. This study highlights the utility of OGM as a diagnostic tool for repeat expansion and contraction diseases such as FA, FXS, EPM1A, and FSHD.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459586","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 Novel PTPRQ c.3697del Variant Causes Autosomal Dominant Progressive Hearing Loss in Both Humans and Mice. 新型 PTPRQ c.3697del 变体导致人类和小鼠常染色体显性进行性听力损失。

IF 2.9 3区医学

Clinical Genetics Pub Date : 2024-10-21 DOI: 10.1111/cge.14634

Yaqi Zhou, Na Yin, Lingchao Ji, Xiaochan Lu, Weiqiang Yang, Weiping Ye, Wenhui Du, Ya Li, Hongyi Hu, Xueshuang Mei

{"title":"A Novel PTPRQ c.3697del Variant Causes Autosomal Dominant Progressive Hearing Loss in Both Humans and Mice.","authors":"Yaqi Zhou, Na Yin, Lingchao Ji, Xiaochan Lu, Weiqiang Yang, Weiping Ye, Wenhui Du, Ya Li, Hongyi Hu, Xueshuang Mei","doi":"10.1111/cge.14634","DOIUrl":"https://doi.org/10.1111/cge.14634","url":null,"abstract":"PTPRQ plays an important role in the development of inner ear hair cell stereocilia. While many autosomal recessive variants in PTPRQ have been identified as the pathogenic cause for nonsyndromic hearing loss (DFNB84A), so far only one autosomal dominant PTPRQ variant, c.6881G>A (p.Trp2294*), has been reported for late-onset, mild-to-severe hearing loss (DFNA73). By using targeted next-generation sequencing, this study identified a novel PTPRQ truncating pathogenic variant, c.3697del (p.Leu1233Phefs*11), from a Chinese Han family that co-segregated with autosomal dominant, postlingual, progressive hearing loss. A Ptprq-3700del knock-in mouse model was generated by CRISPR-Cas9 and characterized for its hearing function and inner ear morphology. While the homozygous knock-in mice exhibit profound hearing loss at all frequencies at the age of 3 weeks, the heterozygous mutant mice resemble the human patients in mild, progressive hearing loss from age 3 to 12 weeks, primarily affecting high frequencies. At this stage, the homozygous knock-in mice have a normal hair cell count but disorganized stereocilia. Cochlear proteosome analysis of the homozygous mutant mice revealed differentially expressed genes and pathways involved in oxidative phosphorylation, regulation of angiogenesis and synaptic vesicle cycling. Our study provides a valuable animal model for further functional studies of the pathogenic mechanisms underlying DFNA73.","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459563","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