A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy
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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.
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.
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 in 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.
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.
KeywordsMitochondrial DNA depletion syndrome 6 (MTDPS6) MPV17 Navajo neurohepatopathy (NNH) Sensorimotor polyneuropathies Whole exome sequencing (WES)
Mitochondrial DNA depletion syndrome 6
Whole exome sequencing
Charcot-Marie-Tooth disease type 2A
Medical research council
Motor conduction velocities
Compound muscle action potentials
Sensory conduction velocities
Sensory nerve action potential
Periodic acid Schiff
Single nucleotide polymorphism
Visual evoked potential
Brainstem auditory evoked potential
Magnetic resonance imaging
This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0135 and HI14C3484) and by the National Research Foundation of Korea (NRF) grants funded by the Korean government, MSIP (NRF-2014R1A2A2A01004240).
- 11.Piekutowska-Abramczuk D, Pronicki M, Strawa K, Karkucińska-Więckowska A, Szymańska-Dębińska T, Fidziańska A, et al. Novel c.191C > G (p.Pro64Arg) MPV17 mutation identified in two pairs of unrelated Polish siblings with mitochondrial hepatoencephalopathy. Clin Genet. 2014;85:573–7.CrossRefPubMedGoogle Scholar
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