一例线粒体DNA缺失综合征8A型家系的RRM2B基因突变检测及生物信息学分析

Detection of RRM2B gene mutation in a mitochondrial DNA deletion syndrome family and Bioinformatics Analysis

目的对一个线粒体DNA缺失综合征8A型(MTDPS8A)家系进行致病基因突变及表型分析。方法应用目标序列捕获加高通量测序技术对1例MDS患者及其父母进行神经肌肉Panel平行测序,在确定先证者的致病基因型后,应用Sanger测序法进行验证,同时检测患者直系亲属的基因型,并用REVEL、MutationTaster与PolyPhen-2软件预测该突变对蛋白功能的影响。结果患者的RRM2B存在罕见的复合杂合错义突变:c.587A>G(p.Y196C)和c.424G>A(p.D142N),导致该基因编码蛋白的第142位和第196位相应氨基酸的改变。这两种突变通过蛋白功能预测都为有害。结论 RRM2B基因的c.424G>A和c.587A>G复合杂合突变很有可能是MDS家系的分子发病原因,此基因型与临床表型有相关的部分。

Objective：To analyze mutations and phenotypes of a mitochondrial DNA deletion syndrome 8 A（MTDPS8A）family. Methods：Target sequence capture high-throughput sequencing technology was used to sequence a case of MDS patients and their parents with neuromuscular Panel.After confirming the pathogenic genotypes of the probands,the Sanger sequencing method was used to verify the results. Genotypes of relatives,and use REVEL,MutationTaster,and PolyPhen-2 software to predict the effect of the mutation on protein function. Results：There were rare compound heterozygous missense mutations in patients with RRM2 B：c.587AG（p.Y196 C）and c.424G〉A（p.D142N）,resulting in the 142 th and 196 th positions of the protein encoded by the gene. The corresponding amino acid changes.Both of these mutations are predicted to be harmful through protein function. Conclusion：The multiple heterozygous mutations of c.424G〉A and c.587AG in RRM2B gene are likely to be the molecular pathogenesis of the MDS family. This genotype is associated with the clinical phenotype.