A novel GDAP1 mutation P78L responsible for CMT4A disease in three Moroccan families.
BACKGROUND
The gene encoding the ganglioside-induced-differentiation-associated protein 1 (GDAP1) has been associated with both axonal and demyelinating neuropathy. Up to date, 25 mutations in the GDAP1 gene have been reported in patients from different origins.


METHODS
Three Moroccan families with early onset ARCMT1 and autosomal recessive inheritance were genotyped to test linkage to 8q21.3 and their GDAP1 gene coding exons screened for mutations.


RESULTS
A novel C233T transversion at codon 78 (P78L) was detected in 6 patients from 3 unrelated families. The mutation was found to be homozygous in two families and compound heterozygous in association with the already reported S194X mutation in one family. The P78L mutation was associated with a common haplotype suggesting a Moroccan founder mutation. The patients had symptoms within the two first years of life and developed common phenotype of CMT4A with evident hoarse-voice in two cases with the longer disease duration.


CONCLUSIONS
P78L mutation was associated with a common haplotype suggesting a common ancestor.
Bouhouche
Ahmed
A
Service de Neurologie et de Neurogénétique, Hôpital des Spécialités, BP 6402, Al Irfane Rabat, Morocco.
Birouk
Nazha
N
Benomar
Ali
A
Ouazzani
Reda
R
Chkili
Taïeb
T
Yahyaoui
Mohamed
M
D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D009018:Morocco / Q000453:epidemiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree
C118663:GDAP protein; D009419:Nerve Tissue Proteins