DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease

Young Bin Hong, Junghee Kang, Ji Hyun Kim, Jinho Lee, Geon Kwak, Young Se Hyun, Soo Hyun Nam, Hyun Dae Hong, Yu Ri Choi, Sung Chul Jung, Heasoo Koo, Ji Eun Lee, Byung Ok Choi, Ki Wha Chung

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36 Scopus citations


Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies. A DGAT2 mutation (p.Y223H) was found in an autosomal dominant axonal CMT family. In the zebrafish larvae, the over-expressed mutant DGAT2 showed an abrogated formation of the bundle of neuronal axons (fascicles) in the trunk at 3 dpf and significantly decreased number of branched axons per fascicle (BPF) in the peripheral nervous system at 15 dpf.

Original languageEnglish
Pages (from-to)473-480
Number of pages8
JournalHuman Mutation
Issue number5
StatePublished - 1 May 2016

Bibliographical note

Publisher Copyright:
© 2016 Wiley Periodicals, Inc.


  • Axonal neuropathy
  • Charcot-Marie-Tooth disease
  • DGAT2
  • Exome
  • Zebrafish


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