A novel autosomal dominant GDAP1 mutation in an Italian CMT2 family

作者：Manganelli Fiore; Pisciotta Chiara; Nolano Maria; Capponi Simona; Geroldi Alessandro; Topa Antonietta; Bellone Emilia; Suls Arvid; Mandich Paola; Santoro Lucio^*

来源：Journal of the Peripheral Nervous System, 2012, 17(3): 351-355.

DOI：10.1111/j.1529-8027.2012.00414.x

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

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.

• 出版日期2012-9