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Background  Mutations in  MPV17  cause the autosomal recessive disorder mitochondrial DNA depletion syndrome 6 (MTDPS6), also called Navajo neurohepatopathy (NNH). Clinical features of MTDPS6 is infantile onset of progressive liver failure with seldom development of progressive neurologic involvement.    Methods  Whole exome sequencing (WES) was performed to isolate the causative gene of two unrelated neuropathy patients (9 and 13 years of age) with onset of the syndrome. Clinical assessments and biochemical analysis were performed.    Results  A novel homozygous mutation (p.R41Q) in  MPV17  was found by WES in both patients. Both showed axonal sensorimotor polyneuropathy without liver and brain involvement, which is neurophysiologically similar to axonal Charcot-Marie-Tooth disease (CMT). A distal sural nerve biopsy showed an almost complete loss of the large and medium-sized myelinated fibers compatible with axonal neuropathy. An i n vitro  assay using mouse motor neuronal cells demonstrated that the abrogation of  MPV17  significantly affected cell integrity. In addition, the expression of the mutant protein affected cell proliferation. These results imply that both the loss of normal function of  MPV17  and the gain of detrimental effects of the mutant protein might affect neuronal function.    Conclusion  We report a novel homozygous mutation in  MPV17  from two unrelated patients harboring axonal sensorimotor polyneuropathy without hepatoencephalopathy. This report expands the clinical spectrum of diseases caused by mutations of  MPV17 , and we recommend  MPV17  gene screening for axonal peripheral neuropathies.    Electronic supplementary material  The online version of this article (doi:10.1186/s12883-015-0430-1) contains supplementary material, which is available to authorized users.

A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy