青岛大学医学院学报2017，Vol.53Issue(4)：379-381,385,4.DOI:10.13361/j.qdyxy.201704001
遗传性痉挛性截瘫新突变的全基因组外显子测序分析
AN ANALYSIS OF A NOVEL MUTATION IN A CHINESE FAMILY WITH HEREDITARY SPASTIC PARAPLEGIAS BY WHOLE EXOME SEQUENCING
摘要
Abstract
Objective To identify the causative gene mutation and explore the genotype-phenotype association through whole exome sequencing (WES) of a Chinese Han family with autosomal dominant hereditary spastic paraplegia (HSP),and to provide a theoretical basis for prenatal diagnosis of HSP.Methods A Chinese Han family with HSP was selected.Neurological examinations were performed on the proband (Ⅳ 11),proband's sister with HSP (Ⅳ 8),and proband's brother without HSP (Ⅳ 9).Genomic DNA was extracted for WES.The suspected gene mutation was subjected to Sanger sequencing among 50 healthy controls as well as 6 patients and 13 normal subjects in the third and fourth generations of this family,and its harm was predicted using DNAMAN software.Results A novel nonsense mutation in exon 14 of the SPG4 (SPAST) gene (c.1606C＞T,p.Gln536X) was found in the 6 patients of this family,but it was not found in the 50 healthy controls and the 13 normal subjects of this family.The DNAMAN analysis identified a single-nucleotide change from C to T causing a substitution from glutamine to an immature stop codon at codon 536.This mutation co-segregated with the phenotype of HSP patients in this family.Conclusion The novel nonsense mutation in the SPG4 gene (c.1606C＞T,p.Gln536X) is the causative mutation in the family with HSP,which provides a basis for prenatal diagnosis of HSP.关键词
痉挛性截瘫,遗传性/全基因组关联研究/外显子/SPG4基因/突变Key words
spastic paraplegia, hereditary/genome-wide association study/exons/genes, SPG4/mutation分类
医药卫生引用本文复制引用
井忠翠,侯华彬,高凯旋,刘静静,刘世国,王海燕..遗传性痉挛性截瘫新突变的全基因组外显子测序分析[J].青岛大学医学院学报,2017,53(4):379-381,385,4.基金项目
国家自然科学基金资助项目(30971586) （30971586）
