Abstract: Objective To identify the mutation of glycogen-branching enzyme 1 (GBE1) gene in a family with glycogen storage disease type Ⅳ(GSD Ⅳ). Methods A 17-month-old Chinese girl was admitted to the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou,China) with hepatosplenomegaly.She had shown signs of jaundice and failure to thrive.The peripheral blood samples from the proband and her parents and two older brothers were collected,and the pathogenic genes and mutational sites of the proband were screened by the next generation sequencing and verified by Sanger sequencing. Results In the family,the proband carried a homozygous mutation of c.1571G>A in the GBE1 gene,while his parents and the younger brother carried a heterozygous mutation of c.1571G>A.The older brother was normal.GSD Ⅳ was diagnosed and liver transplantation was recommended.The parents declined the liver transplantation.She died of liver failure at 22 months of age. Conclusions The clinical characteristics and gene mutation analysis of one pedigree with GSD Ⅳ and homozygous missense c.1571G>A mutation in GBE1 gene were first identified in mainland China.The identified mutations add to the list of GBE1 mutations of the hepatic form of GSD-IV.

Key words: glycogen storage disease type Ⅳ, next generation sequencing, glycogen-branching enzyme 1 gene

摘要： 目的 研究1例糖原累积病Ⅳ型(GSD Ⅳ)患者及其家系的基因突变情况。方法 患儿,女,1岁5个月,因轻度黄疸,肝脾肿大2月,生长迟缓1年就诊。采集该家系先证者及其父母,两个哥哥的外周血,采用二代测序方法查找先证者致病基因及突变位点,Sanger测序进行突变验证。结果 该家系先证者为GBE1基因c.1571G>A纯合错义突变,双亲及一个哥哥为GBE1基因c.1571G>A杂合错义突变,另一个哥哥基因检测未见该突变,确诊为GSD Ⅳ型,建议行肝移植治疗,因家属拒绝,患儿于生后22个月死亡。结论 首次在国内报道了GSD Ⅳ型的家系及其分子遗传情况以及GBE1基因c.1571G>A纯合突变,丰富了GSD Ⅳ型在中国人群的突变谱。

关键词: 糖原累积病Ⅳ型, 二代测序, GBE1基因