Abstract: 　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.

Key words: 　mitochondrial disease;　POLG gene;　pedigree analysis;　sensory neuropathy;　epilepsy