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Hum Mutat. 2016 May;37(5):473-80. doi: 10.1002/humu.22959. Epub 2016 Feb 9.

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

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Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
Neuroscience center, Samsung Medical Center, Seoul, South Korea.
Department of Biological Sciences, Kongju National University, Gongju, South Korea.
Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, South Korea.
Department of Pathology, Ewha Womans University School of Medicine, Mokdong Hospital, Seoul, South Korea.
SGI, Samsung Medical Center, Seoul, South Korea.
Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, South Korea.


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.


Charcot-Marie-Tooth disease; DGAT2; axonal neuropathy; exome; zebrafish

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