A novel GDAP1 mutation 439delA is associated with autosomal recessive CMT disease.

BACKGROUND Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Based on neurophysiological and neuropathological criteria CMT has been sub-classified into two main types: demyelinating and axonal. Furthermore, it is genetically heterogeneous with autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance. Thus far, seven genes have been identified in association with the demyelinating AR-CMT disease. We hereby report our clinical and molecular genetic findings in a consanguineous family with AR-CMT. METHODS Two young sisters with AR-CMT and other non-affected family members were clinically and electrophysiologically evaluated and then molecular genetic investigation was carried out in order to identify the pathogenic mutation. RESULTS Following an initial indication for linkage of the family to the CMT4A locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and identified a single nucleotide deletion in exon 3 that is associated with AR-CMT in the family. CONCLUSIONS We identified a novel GDAP1 439delA mutation that is associated with AR-CMT in a consanguineous family of Iranian descent with two affected young girls and a history in other members of the family.