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KMID : 1161520130170040228
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Animal Cells and Systems
2013 Volume.17 No. 4 p.228 ~ p.236
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Missense mutations of mitofusin 2 in axonal Charcot?Marie?Tooth neuropathy: polymorphic or incomplete penetration?
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Nakhro Khriezhanuo
Park Jin-Mo
Choi Byung-Ok
Chung Ki-Wha
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Abstract
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Charcot?Marie?Tooth disease type 2A (CMT2A), which is caused by mutations in the Mitofusin 2 (MFN2) gene, is an axonal defective type of peripheral neuropathy. Over the years, mutations in the MFN2 have been reported to produce a wide range of phenotypes. This study endeavors to interrogate the phenomenon of penetrance and expressivity in MFN2 mutations for CMT2 families, showing both normal and disease phenotypes in mutant carriers within the same family. Exome sequencing was performed for four CMT2 families that showed three noncosegregating MFN2 missense mutations: p.R280H, p.R259H, and p.K98Q. The p.R280H mutation has been reported as disease causing by several studies, while two other mutations are unreported. Analysis of the exome data for more than 60 CMT-related genes did not produce other qualifying candidate mutations for the specific phenotypes. Commendable in silico scores were obtained, and control samples showed no mutation. The occurrence of incomplete penetrance has not been documented for MFN2 prior, but these families' attributes and also the phenotypic heterogeneity reported over the years suggest the involvement of incomplete penetrance and variable expressivity in the MFN2 gene. Despite these predispositions, we also question if these variants are just very rare polymorphisms.
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KEYWORD
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Charcot-MarieTooth disease type 2A, MFN2, incomplete penetrance, polymorphism
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