A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family

Fiore Manganelli, Chiara Pisciotta, Maria Nolano, Simona Capponi, Alessandro Geroldi, Antonietta Topa, Emilia Bellone, Arvid Suls, Paola Mandich, Lucio Santoro

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)351-355
Number of pages5
JournalJournal of the Peripheral Nervous System
Volume17
Issue number3
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Charcot-Marie-Tooth disease
  • GDAP1
  • neurophysiology
  • skin biopsy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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