Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt
Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt
复制标题
DOI：
10.1136/jmedgenet-2015-103511
复制
发表时间：
2016-06-01
影响因子：
4
通讯作者：
Rump, Andreas
中科院分区：
文献类型：
--
作者：
Di Donato, Nataliya;Neuhann, Teresa;Rump, Andreas
背景视网膜色素变性合并听力损失可能是不同孟德尔疾病的特征。我们描述了一种新的综合征引起的双等位基因突变的'exosome组件2'（EXOSC 2）gene.Methods临床确诊的三个类似的受影响的患者，其次是全外显子测序。结果三个人从两个无关的德国家庭提出了一种新的孟德尔疾病，包括儿童近视，早发性视网膜色素变性，进行性感音神经性听力损失，甲状腺功能减退，身材矮小，短指，可识别的面部完形、过早衰老和轻度智力残疾。全外显子组测序显示所有3例患者的EXOSC 2基因中存在纯合或复合杂合错义变体。EXOSC 2编码“核糖体RNA加工蛋白4”（RRP 4）-RNA外泌体的核心组分之一。RNA外泌体是一种多蛋白复合物，在RNA加工和降解中起关键作用。有趣的是，EXOSC 2相关的表型与先前报道的与RNA外泌体核心组分基因EXOSC 3和EXOSC 8突变相关的疾病只有很小的重叠。结论我们报告了一种可能由RNA外泌体功能改变引起的新疾病，扩大了RNA代谢受损的临床后果范围。
Background 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.Methods Clinical ascertainment of three similar affected patients followed by whole exome sequencing.Results 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.Conclusion 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.