title: A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family.
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.
authors.affiliation: Department of Neurological Sciences, University Federico II of Naples, Naples, Italy.
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Pisciotta
authors.forename: Maria
authors.initials: M
authors.lastname: Nolano
authors.forename: Simona
authors.initials: S
authors.lastname: Capponi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Geroldi
authors.forename: Antonietta
authors.initials: A
authors.lastname: Topa
authors.forename: Emilia
authors.initials: E
authors.lastname: Bellone
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins