Title
|
|
|
|
A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
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. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
Journal of the peripheral nervous system. - -
| |
Publication
|
|
|
|
Oxford
,
2012
| |
ISSN
|
|
|
|
1085-9489
| |
DOI
|
|
|
|
10.1111/J.1529-8027.2012.00414.X
| |
Volume/pages
|
|
|
|
17
:3
(2012)
, p. 351-355
| |
ISI
|
|
|
|
000308712000007
| |
Full text (Publisher's DOI)
|
|
|
|
| |
Full text (publisher's version - intranet only)
|
|
|
|
| |
|