1个GM1神经节苷脂贮积症合并杜氏肌营养不良症家系的遗传学病因分析

Genetic analysis of a pedigree affected with GM1 gangliosidosis comorbid with Duchenne muscular dystrophy

目的分析1个GM1神经节苷脂贮积症合并杜氏肌营养不良症家系的遗传学病因。方法运用高通量测序技术、一代测序技术、染色体微阵列分析技术、多重连接探针扩增技术等对该病例及其家系成员进行联合基因检测。结果基因检测结果提示,先证者GLB1基因存在c.446C>T(p.S149F)和c.1214C>T(p.T405I)复合杂合突变,两个突变分别来自于父亲(c.1214C>T)和母亲(c.446C>T),胎儿未见GLB1基因突变,但存在DMD基因第49号外显子缺失,来源于母亲。结论GLB1基因c.446C>T和c.1214C>T的复合杂合突变可能是本例患儿的致病原因,多种基因检测技术手段的联合应用可以提高基因变异的检出率,减少出生缺陷的发生,为产前诊断及遗传咨询提供新的方案思路。

Objective To analyze the genetic etiology of a GM1 ganglioside storage syndrome family with Duchenne muscular dystrophy.Methods Next-generation sequencing,first-generation sequencing,chromosome microarray analysis,and multiplex ligation probe amplification technology were used to test the family members.Results The genetic test results suggest that the proband's GLB1 gene had c.446C>T(p.S149F)and c.1214C>T(p.T405I)heterozygous mutations,two mutations respectively from his father(c.1214C>T)and mother(c.446C>T).The fetus had no GLB1 gene mutation,but has a deletion of the DMD gene in exon 49,origined from his mother.Conclusion The complex heterozygous mutations c.446C>T and c.1214C>T of GLB1 gene may be the pathogenic cause of the child.The combined application of multiple gene detection techniques can improve the detection rate of gene mutations and reduce the birth defects and provide a new approach to genetic counseling.