Autosomal Recessive CMT: A novel GDAP1 mutation 439delA

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Can J Neurol Sci. 2006 Aug;33(3):311-6.

A novel GDAP1 mutation 439delA is associated with autosomal recessive

CMT disease.

Georgiou DM, Nicolaou P, Chitayat D, Koutsou P, Babul-Hirji R, Vajsar

J, J, Christodoulou K.

Molecular Genetics Department D, The Cyprus Institute of Neurology

and Genetics, Nicosia, Cyprus.

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.