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.
Georgiou
Domna-Maria
DM
Molecular Genetics Department D, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Nicolaou
Paschalis
P
Chitayat
David
D
Koutsou
Pantelitsa
P
Babul-Hirji
Riyana
R
Vajsar
Jiri
J
Murphy
Jillian
J
Christodoulou
Kyproula
K
D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D002898:Chromosomes, Human, Pair 8; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D007492:Iran; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree
C118663:GDAP protein; D009419:Nerve Tissue Proteins