HEXA基因纯合变异致Tay-Sachs病1例

A case of Tay-Sachs disease caused by homozygous mutation of HEXA gene

目的 分析由HEXA基因纯合变异引起Tay-Sachs病的临床特点及遗传学特征。方法 回顾分析1例Tay-Sachs病患儿的临床资料及基因检测结果。结果 患儿,男,2岁,精神运动发育倒退(4月龄能抬头,7月龄会翻身,8月龄会坐,10月龄左右可发单音节词,14月龄突然不能发单音节词,现不能爬、独自站立、行走),1岁11月时出现抽搐,反复间断抽搐1月余。全外显子组测序显示HEXA基因(NM_000520.4)存在c.532C>T(p.R178C)纯合变异,来源于父母,该变异判定为“致病”。HEXA基因(NM_000520.4)c.532C>T(p.R178C)纯合变异,在东亚人群频率为0,未见文献报道。结论 基因检测有助于Tay-Sachs病的早期诊断,本病例进一步扩展了东亚人群HEXA的基因突变谱。

Objective To analyze the clinical manifestations and genetic characteristics of Tay-Sachs disease caused by homozygous mutation of HEXA gene.Methods The clinical data and genetic test results of a child with Tay-Sachs disease were retrospectively analyzed.Results The child,male,2 years old,showed psychomotor retardation(At the age of 4 months,he can raise his head,at 7 months he can turn over,at 8 months he can sit,at the age of 10 months,he can pronounce monosyllables,but suddenly he can’t pronounce monosyllables at the age of 14 months.It is now impossible to crawl,stand or walk alone).She had seizures at the age of 1 year and 11 months and had repeated seizures for more than 1 month.Whole-exome sequencing revealed a homozygous c.532C>T(p.R178C)mutation in the HEXA gene(NM_00052.4)originating from the parents,which was determined to be“pathogenic”.Homozygous mutation of HEXA gene(NM_00052.4)c.532C>T(p.R178C),with a frequency of 0 in East Asian population,has not been reported in the literature.Conclusion Genetic testing is helpful for the early diagnosis of Tay-Sachs disease.This case further expands the HEXA gene mutation spectrum in East Asian population.