DGAT2 Mutation in a Family with Autosomal Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease
- Hong, Y.B., Kang, J., Kim, J.H., Lee, J., Kwak, G., Hyun, Y.S., Nam, S.H., Hong, H.D., Choi, Y.R., Jung, S.C., Koo, H., Lee, J.E., Choi, B.O., Chung, K.W.
- Human Mutation 37(5): 473-80 (Journal)
- Registered Authors
- Lee, Ji Eun
- Charcot-Marie-Tooth, DGAT2, axonal neuropathy, exome, zebrafish
- MeSH Terms
- Age of Onset
- Cell Line
- Cell Proliferation
- Charcot-Marie-Tooth Disease/genetics*
- Charcot-Marie-Tooth Disease/metabolism
- Charcot-Marie-Tooth Disease/pathology
- Diacylglycerol O-Acyltransferase/genetics*
- Diacylglycerol O-Acyltransferase/metabolism*
- Genetic Predisposition to Disease
- Motor Neurons/cytology
- Motor Neurons/metabolism
- Mutation, Missense*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- 26786738 Full text @ Hum. Mutat.
Hong, Y.B., Kang, J., Kim, J.H., Lee, J., Kwak, G., Hyun, Y.S., Nam, S.H., Hong, H.D., Choi, Y.R., Jung, S.C., Koo, H., Lee, J.E., Choi, B.O., Chung, K.W. (2016) DGAT2 Mutation in a Family with Autosomal Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease. Human Mutation. 37(5):473-80.
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 over-expression 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. This article is protected by copyright. All rights reserved.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes