色素性视网膜炎
遗传学
外小体复合体
外显子组测序
生物
听力损失
身材矮小
错义突变
外显子组
感音神经性聋
复合杂合度
智力残疾
突变
核糖核酸
医学
基因
内分泌学
非编码RNA
听力学
作者
Nataliya Di Donato,Teresa Neuhann,Anne-Karin Kahlert,Barbara Klink,Karl Hackmann,Irmingard M. Neuhann,Barbora Novotná,Jens Schallner,C. Krause,Ian A. Glass,Shawn E. Parnell,Anna Benet‐Pagès,Anke M. Nissen,Wolfgang Berger,Janine Altmüller,Holger Thiele,Bernhard H. F. Weber,Evelin Schröck,William B. Dobyns,August Bier,Andreas Rump
标识
DOI:10.1136/jmedgenet-2015-103511
摘要
Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene.Clinical ascertainment of three similar affected patients followed by whole exome sequencing.Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8.We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism.
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