RNU4ATAC变异导致Joubert综合征伴骨骼受累的进一步证据。

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Fulvio D'Abrusco, Simone Gana, Enrico Alfei, Emanuela Scarano, Francesco Nicita, Enrico Silvio Bertini, Maria Cristina Digilio, Ginevra Zanni, Domenico Barbuti, Eleonora Carlicchi, Anna Pichiecchio, Stefano D'Arrigo, Valentina Serpieri, Enza Maria Valente
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引用次数: 0

摘要

RNU4ATAC是一个参与小剪接体的非编码基因,在一系列隐性遗传的综合征性骨骼疾病中发生突变。最近,在5例患者中检测到双等位基因RNU4ATAC致病变异,这些患者表现出复杂的综合征表型和类似“臼齿征”(MTS)的脑畸形。这是Joubert综合征(JS)的标志,这是一种多器官受累的神经发育性纤毛病。我们重新分析了53例JS患者的外显子组测序(ES),这些患者缺乏已知JS相关基因的编码变体。3个先证者复合杂合性鉴定出4个RNU4ATAC变异(n.16G>A、n.51G>A、n.13C>T和n.30G>A),占阴性病例的5.6%。所有患者均表现出与JS和rnu4atac相关骨骼疾病重叠的MTS和临床特征。这些发现扩大了rnu4atac相关疾病的表型谱,包括复杂的神经-骨骼纤毛病表型,并强调了ES再分析发现常规诊断无法检测到的非编码变异的相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement.

RNU4ATAC is a non-coding gene involved in the minor spliceosome, and is mutated in a spectrum of syndromic skeletal disorders with recessive inheritance. Recently, biallelic RNU4ATAC pathogenic variants were detected in five patients presenting a complex syndromic phenotype and a brain malformation resembling the 'molar tooth sign' (MTS). This is the hallmark of Joubert syndrome (JS), a neurodevelopmental ciliopathy with multiorgan involvement.We reanalysed exome sequencing (ES) from 53 patients with JS, who lacked coding variants in known JS-associated genes. Four RNU4ATAC variants (n.16G>A, n.51G>A, n.13C>T and n.30G>A) were identified in compound heterozygosity in three probands, accounting for 5.6% of negative cases. All patients displayed the MTS and clinical features overlapping those of JS and RNU4ATAC-related skeletal disorders.These findings expand the phenotypic spectrum of RNU4ATAC-related disorders to include a complex neurological-skeletal ciliopathy phenotype, and highlight the relevance of ES reanalysis to uncover non-coding variants often undetected by conventional diagnostics.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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