To report the clinical features, myopathological changes, and gene mutations in five Chinese patients with mitochondrial diseases caused by POLG gene mutations.

Clinical materials of five unrelated patients who were referred to Department of Neurology, Peking University First Hospital from April 2012 to January 2018, carrying POLG gene mutations, were retrospectively analyzed. Muscle/nerve biopsies and targeted second-generation gene sequencing were performed on the patients.

Among the five patients, three were male and two were female. Two cases were dominant inheritance and three were sporadic or recessive inheritance. The ages of onset were from 15 to 40 years with disease course of one to 26 years. One of them showed atypical SANDO (sensory ataxic neuropathy, dysarthria, and ophthalmoparesis) syndrome accompanied by cardiac preexcitation syndrome. There were two cases with autosomal dominant and one case with recessive progressive external ophthalmoplegia plus syndrome. One case presented with cognitive delay and sensory neuropathy. The pathological changes of mitochondrial myopathy were observed in all four patients with muscle involvement. Sural nerve biopsy in the patient with cognitive delay and sensory ataxia revealed chronic axonal pathological changes. POLG gene mutations were found in all five patients by targeted next generation sequencing, including single heterozygous mutations in two dominant inherited patients (c.914 G>A and c.2864A>G, respectively), and compound heterozygous POLG gene mutations in the other three sporadic/recessive inherited patients (c.2591 A>G/c.1790 G>A, c.924G>T/c.3002delG and c.1613A>T/c.1612 G>T, respectively). There were six novel mutations not reported before, i.e., 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.

POLG gene mutations can lead to different clinical spectrums. Progressive external ophthalmoplegia, limb weakness and axonal sensory neuropathy are common presentations in this group of patients with POLG gene related mitochondrial neuromuscular diseases. Novel mutations found in this study expand the mutational spectrum of POLG gene.

Mitochondrial disease; DNA polymerase gamma; POLG gene; Progressive external ophthalmoplegia; Axonal sensory neuropathy