A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family
We report the clinical, electrophysiological, and skin biopsy findings of an Italian Charcot‐Marie‐Tooth disease type 2 (CMT2) family with a novel heterozygous GDAP1 mutation. We observed a marked intra‐familial phenotypic variability, in age at onset and disease severity which ranged from a typical CMT phenotype to an asymptomatic status. Electrophysiological study, consistent with an axonal sensory‐motor neuropathy, confirmed a different degree of severity and disclosed minimal electrophysiological abnormalities also in the asymptomatic subjects. Skin biopsy findings showed a variable loss of large and small somatic nerve fibers. Molecular analysis identified a novel heterozygous missense mutation (Arg120Gly) in the GDAP1 gene which co‐segregated with the disease within the pedigree. In conclusion, our findings confirm that the GDAP1 autosomal dominant mutations underlie a pronounced phenotypic variability, mimicking the effects of reduced penetrance. Notably, electrophysiological study in this family allowed to reveal hidden positive family history and assess a dominant inheritance pattern, revealing subclinical neuropathy in asymptomatic mutation carriers.
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Document Type: Research Article
Publication date: September 1, 2012