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

Title
A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy
Authors
ChoiY.-R.HongY.B.JungS.-C.LeeJ.H.KimY.J.ParkH.J.J.KooH.J.-S.JwaD.H.N.WooS.-Y.S.-B.ChungK.W.B.-O.
Ewha Authors
구혜수우소연정성철박형준
SCOPUS Author ID
구혜수scopus; 우소연scopus; 정성철scopus; 박형준scopusscopus
Issue Date
2015
Journal Title
BMC Neurology
ISSN
1471-2377JCR Link
Citation
vol. 15, no. 1
Keywords
Mitochondrial DNA depletion syndrome 6 (MTDPS6)MPV17Navajo neurohepatopathy (NNH)Sensorimotor polyneuropathiesWhole exome sequencing (WES)
Publisher
BioMed Central Ltd.
Indexed
SCIE; SCOPUS WOS scopus
Abstract
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 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. 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. © 2015 Choi et al.
DOI
10.1186/s12883-015-0430-1
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의학전문대학원 > 의학과 > Journal papers
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