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Title
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A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Journal of the peripheral nervous system. - -
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Publication
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Oxford
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2012
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ISSN
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1085-9489
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Volume/pages
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17
:3
(2012)
, p. 351-355
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ISI
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000308712000007
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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