Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene.
BACKGROUND
The first locus for demyelinating autosomal recessive Charcot-Marie-Tooth (ARCMT) disease was identified in 8q13, where mutations in GDAP1 have been found. Mutations in the same gene have been detected in families with axonal ARCMT disease.


OBJECTIVE
To determine the clinical, electrophysiologic, and morphologic characteristics of a consanguineous Moroccan family with ARCMT disease associated with the S194X mutation in the GDAP1 gene.


METHODS
Four patients from a consanguineous Moroccan family were examined clinically and electrophysiologically. In one patient, a morphometric and ultrastructural study of a peroneal nerve biopsy sample was performed. Mutation in the coding region of the GDAP1 gene was identified by direct sequencing.


RESULTS
Neuropathy was evident early in childhood, walking was delayed in one patient, and onset of symptoms occurred before 18 months in the others. The phenotype was severe: foot deformities and disabilities involving the hands and feet developed toward the end of the first decade, followed by involvement of proximal muscles in the lower limbs, leading to loss of autonomy. Electrophysiologic findings were consistent with an axonal form of CMT disease: motor nerve conduction velocities, recordable in one patient only, were greater than 40 m/sec. Sensory nerve action potentials were either abolished or substantially reduced in amplitude. The morphologic data supported the diagnosis of axonal neuropathy, showing a marked reduction in myelinated fibers and signs of axonal regeneration, including frequent pseudo-onion bulb formations. The 4 patients in this family were homozygous for the S194X mutation in the GDAP1 gene.


CONCLUSIONS
Electrophysiologic and pathological findings support the hypothesis of an axonal disorder in this ARCMT family with the S194X mutation in the GDAP1 gene.
Birouk
Nazha
N
Service de Neurologie, Hôpital des Spécialités, Rabat, Morocco. birna@iam.net.ma
Azzedine
Hamid
H
Dubourg
Odile
O
Muriel
Marie-Paule
MP
Benomar
Ali
A
Hamadouche
Tarik
T
Maisonobe
Thierry
T
Ouazzani
Reda
R
Brice
Alexis
A
Yahyaoui
Mohamed
M
Chkili
Taïb
T
Le Guern
Eric
E
D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D009018:Morocco / Q000208:ethnology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012694:Serine / Q000235:genetics
D012694:Serine