一个亚历山大病家系的临床特点和GFAP基因变异分析

Analysis of clinical characteristics and genetic variation of GFAP in an Alexander disease pedigree

目的探讨GFAP基因变异导致亚历山大病的临床表现及基因变异特点。方法分析一家系母女2例亚历山大病患者的临床资料、实验室检查、影像学检查,并采用高通量二代测序和Sanger验证技术,进行GFAP基因变异检测。结果基因检测发现,该家系母女2例患者的GFAP基因均存在c.262C>T的杂合突变,而该家系其他正常成员均未见基因突变,表明患儿母亲GFAP基因变异为新发突变,而患儿c.262C>T突变遗传自其母亲,且GFAP基因变异为已知致病性变异,具有家族遗传性。结合患儿临床表现及影像学检查,该家系母女2例患者均明确诊断为Ⅱ型亚历山大病,该家系证实为Ⅱ型亚历山大病家系。结论 GFAP基因杂合变异是亚历山大病家系的遗传学特点,并且同一亚历山大病家系中不同患者的临床表型差异较大。

Objective To explore the clinical features and gene variation characteristics of Alexander disease caused by GFAP gene mutation.Methods The clinical data,laboratory examination,and imaging examination of 2 patients with Alexander’s disease from a mother and daughter were retrospectively analyzed.High throughput sequencing and Sanger validation were used to detect GFAP gene variation.Results Genetic testing showed that the GFAP gene of both the mother and the daughter of the two patients had c.262 C> T heterozygous mutation,while other normal members of the family had no gene mutation,indicating that the GFAP gene mutation of the daughter’s mother was a new mutation,while the daughter’s c.262 C> T mutation was inherited from her mother,and the GFAP gene mutation was a known pathogenic mutation,which may be familial.Combining with the patients clinical manifestation and imaging examination,the family of 2 cases,the mother and the daughter were both diagnosed as Alexander diseasetype Ⅱ,and the family was diagnosed as Alexander’s disease type Ⅱ pedigree.Conclusion Heterozygous variation of GFAP gene is a genetic characteristic of Alexander’s families,and the clinical phenotypes of different patients in Alexander’s famlies differ greatly.