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. Conclusion: 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.