title: A novel homozygous MPV17 mutation in two families with axonal sensorimotor polyneuropathy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. power_upup@naver.com.
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Choi
authors.affiliation: Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul, Korea. youngbinhong@gmail.com.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. jungsc@ewha.ac.kr.
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
authors.affiliation: Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. wkgustmxk57@nate.com.
authors.forename: Ja Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. yjinnim11@nate.com.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea. sigund@hanmail.net.
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. nrjinholee@gmail.com.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea. heasoo@ewha.ac.kr.
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. jisulee251@gmail.com.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. donghwan89@naver.com.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Jwa
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea. prettycy@naver.com.
authors.forename: Namhee
authors.initials: N
authors.lastname: Jung
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea. soyounwoo@ewha.ac.kr.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
authors.affiliation: Department of Neurology, Kyung Hee University, College of Medicine, Seoul, Korea. oldkino@naver.com.
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Kongju National University, 56 Gonjudaehak-ro, Gongju, Chungnam, 314-701, Korea. kwchung@kongju.ac.kr.
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, Seoul, 135-710, Korea. bochoi77@hanmail.net.|Neuroscience center, Samsung Medical Center, Seoul, Korea. bochoi77@hanmail.net.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011115:Polyneuropathies / Q000235:genetics*; D056910:Republic of Korea
chemical_list: C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins