A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease

A wide range of phenotypes have been reported in autosomal recessive (AR) Charcot-Marie-Tooth disease (CMT) patients carrying mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene, such as axonal, demyelinating, and intermediate forms of AR CMT. There have been very few reports of GDAP1 mutations in autosomal dominant (AD) CMT. Here, we report an AD CMT family with a novel Q218E mutation in the GDAP1 gene. The mutation was located within the well-conserved glutathione S-transferase (GST) core region and co-segregated with the affected members in the pedigree. The affected AD CMT individuals had a later disease onset and much milder phenotypes than the AR CMT patients, and the histopathologic examination revealed both axonal degeneration and demyelination.