目的　分析POLG基因变异致线粒体病的临床表型及基因变异。方法　回顾分析于2019年5月就诊，并经 采集外周血DNA进行医学外显子、外显子-内含子交界区靶向二代测序和一代验证， 1个确诊为POLG基因变异致线粒体 病家系的临床资料。结果　先证者，男，10岁，与其同卵双胎哥哥均有相同的体征，深感觉受损、腱反射消失、肌肉可疑萎 缩。先证者3个兄姐先后于1岁多夭折。提取患儿及其父母的外周血，先证者及同卵双胎哥哥POLG基因均存在G.2558>A （p.R853Q）、c.2890>T（p.R964C）复合杂合变异，分别来源于患儿父母亲。结论　POLG基因复合杂合变异线粒体病家系 成员有不同的表型；POLG相关疾病，即使同种基因变异，其临床异质性也较大。

　Objective　To explore the clinical phenotype and gene variation of patients with mitochondrial disease caused by POLG gene variation in a family. Methods　The clinical data of a patient diagnosed with mitochondrial disease caused by POLG gene mutation in May 2019 were analyzed retrospectively. The peripheral blood DNA was collected for next generation sequencing (NGS), and Sanger sequencing was performed to verify the variations detected by NGS. Results The proband, a 10-year-old boy, had the same physical signs as his twin elder brother, including deep sensory impairment, disappearance of tendon reflex, and suspected muscular atrophy. Three elder brothers and elder sisters of the proband died in their first years. Blood samples were collected from family members, including the proband’s parents and siblings. Two compound heterozygous variations of c.2558 G >A (p.R853Q) and c.2890>T (p.R964C) in POLG gene were found in both the proband and his living twin elder brother, which inherited form both of their father and mother, respectively. Conclusions　Phenotypes are different among the family members of mitochondrial disease with POLG gene mutations. The clinical heterogeneity of POLG-related diseases is great even with same variation.