BMC Neurology

, 15:179 | Cite as

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

  • Yu-Ri Choi
  • Young Bin Hong
  • Sung-Chul Jung
  • Ja Hyun Lee
  • Ye Jin Kim
  • Hyung Jun Park
  • Jinho Lee
  • Heasoo Koo
  • Ji-Su Lee
  • Dong Hwan Jwa
  • Namhee Jung
  • So-Youn Woo
  • Sang-Beom Kim
  • Ki Wha Chung
  • Byung-Ok Choi
Research article



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.


Mitochondrial DNA depletion syndrome 6 (MTDPS6) MPV17 Navajo neurohepatopathy (NNH) Sensorimotor polyneuropathies Whole exome sequencing (WES) 



Mitochondrial DNA depletion syndrome 6


Navajo neurohepatopathy


Whole exome sequencing


Oxidative phosphorylation


Mitochondrial DNA


Charcot-Marie-Tooth disease


Charcot-Marie-Tooth disease type 2A


Medical research council


Motor conduction velocities


Compound muscle action potentials


Sensory conduction velocities


Sensory nerve action potential


NADH-tetrazolium reductase


Succinate dehydrogenase


Periodic acid Schiff


Single nucleotide polymorphism


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


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).

Supplementary material

12883_2015_430_MOESM1_ESM.docx (44 kb)
Additional file 1: Table S1. List of primers and siRNAs. Table S2. Summary of exome sequencing data. Table S3. List of CMT- and MTDPS- related genes. Table S4. Polymorphic nonsynonymous variants in peripheral neuropathy- and mitochondrial DNA depletion syndrome- related genes from the exome date. (DOCX 43 kb)
12883_2015_430_MOESM2_ESM.tiff (2.8 mb)
Additional file 2: Figure S1. (a) Changes in the mitochondrial OXPHOS system. Western blotting using OXPHOS detection cocktail antibody was performed after knockdown of MPV17. Data are presented as mean ± SEM. *, p < 0.05; **, p < 0.01. (b) Mitochondrial DNA (mtDNA) depletion assay. HEK293 cells were treated with control (pCMV-myc), wild-type or mutant MPV17 transcripts for 72 days, then total DNA was purified and mtDNA depletion was analyzed by comparing the ratio of genomic DNA (beta actin) and mtDNA (ND1 and COX1) using realtime PCR. (c) Overexpression of mutant proteins affected cell proliferation of NSC34. Both MPV17 mutant proteins, R41Q and R41W, affected cell proliferation. (TIFF 2825 kb)


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Copyright information

© Choi et al. 2015

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Yu-Ri Choi
    • 1
  • Young Bin Hong
    • 2
  • Sung-Chul Jung
    • 1
  • Ja Hyun Lee
    • 3
  • Ye Jin Kim
    • 3
  • Hyung Jun Park
    • 4
  • Jinho Lee
    • 5
  • Heasoo Koo
    • 6
  • Ji-Su Lee
    • 5
  • Dong Hwan Jwa
    • 5
  • Namhee Jung
    • 1
  • So-Youn Woo
    • 7
  • Sang-Beom Kim
    • 8
  • Ki Wha Chung
    • 3
  • Byung-Ok Choi
    • 5
    • 9
  1. 1.Department of BiochemistryEwha Womans University School of MedicineSeoulKorea
  2. 2.Stem Cell & Regenerative Medicine Center, Samsung Medical CenterSeoulKorea
  3. 3.Department of Biological ScienceKongju National UniversityGongjuKorea
  4. 4.Department of NeurologyEwha Womans University School of MedicineSeoulKorea
  5. 5.Department of Neurology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  6. 6.Department of PathologyEwha Womans University School of MedicineSeoulKorea
  7. 7.Department of MicrobiologyEwha Womans University School of MedicineSeoulKorea
  8. 8.Department of NeurologyKyung Hee University, College of MedicineSeoulKorea
  9. 9.Neuroscience center, Samsung Medical CenterSeoulKorea

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