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BMC Neurol. 2015 Oct 5;15:179. doi: 10.1186/s12883-015-0430-1.

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

Author information

1
Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. power_upup@naver.com.
2
Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul, Korea. youngbinhong@gmail.com.
3
Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. jungsc@ewha.ac.kr.
4
Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. wkgustmxk57@nate.com.
5
Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. yjinnim11@nate.com.
6
Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea. sigund@hanmail.net.
7
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. nrjinholee@gmail.com.
8
Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea. heasoo@ewha.ac.kr.
9
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. jisulee251@gmail.com.
10
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. donghwan89@naver.com.
11
Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. prettycy@naver.com.
12
Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea. soyounwoo@ewha.ac.kr.
13
Department of Neurology, Kyung Hee University, College of Medicine, Seoul, Korea. oldkino@naver.com.
14
Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. kwchung@kongju.ac.kr.
15
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. bochoi77@hanmail.net.
16
Neuroscience center, Samsung Medical Center, Seoul, Korea. bochoi77@hanmail.net.

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.

PMID:
26437932
PMCID:
PMC4595119
DOI:
10.1186/s12883-015-0430-1
[Indexed for MEDLINE]
Free PMC Article

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