TY - JOUR
T1 - A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family
AU - Manganelli, Fiore
AU - Pisciotta, Chiara
AU - Nolano, Maria
AU - Capponi, Simona
AU - Geroldi, Alessandro
AU - Topa, Antonietta
AU - Bellone, Emilia
AU - Suls, Arvid
AU - Mandich, Paola
AU - Santoro, Lucio
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Charcot-Marie-Tooth disease
KW - GDAP1
KW - neurophysiology
KW - skin biopsy
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UR - http://www.scopus.com/inward/citedby.url?scp=84866346208&partnerID=8YFLogxK
U2 - 10.1111/j.1529-8027.2012.00414.x
DO - 10.1111/j.1529-8027.2012.00414.x
M3 - Article
C2 - 22971097
AN - SCOPUS:84866346208
VL - 17
SP - 351
EP - 355
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
SN - 1085-9489
IS - 3
ER -