MITOCHONDRIAL DISEASES (Posters): P.188Novel POLG mutations and variable clinical phenotypes in 5 Chinese patients with mitochondrial diseases

Abstract

POLG related mitochondrial disorders has rarely been reported in China. Here we report 5 unrelated Chinese patients (2 males and 3 females) with mitochondrial disease caused by POLG gene mutations. Two of them had a dominant family history and 3 were sporadic cases. The ages of onset were from 15 to 40 years old, with disease course ranging from 1 to 26 years. Clinically, 1 case were conformed with SANDO (sensory ataxic neuropathy, dysarthria and ophthalmoparesis) syndrome, 2 cases with autosomal dominant progressive external ophthalmoplegia (PEO), 1 case with autosomal recessive PEO, and 1 case with sensory axonal neuropathy and mental retardation. Laboratory examination revealed normal or mild elevation of serum creatine kinase level. Electromyography revealed myopathic or neurogenic pattern. Nerve conduction studies showed decreased amplitude of nerve action potential in 3 cases, with sensory nerve predominantly involved. Mitochondrial abnormality appeared in 4 patients who underwent muscle biopsies. Sural nerve biopsy revealed chronic axonal neuropathy in the patient with sensory axonal neuropathy and mental retardation. Genetic test revealed compound heterozygous POLG mutations in 3 sporadic patients and single heterozygous mutations in 2 dominant inherited patients. c.914G>A (p.S305N), c.924G>T (p.Q308H), c.1613A>T (p.E538V), c.1612G>T (p.E538*), c.1790 G>A (p.R597Q) and c.3002delG. were novel mutations. Novel mutations found in this study expanded the mutational spectrum of POLG.