Identification of novel GDAP1 mutations causing autosomal recessive CMT in 3 fam

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(Oral presentation at Antwerp Consortium July 2009)

Identification of novel GDAP1 mutations causing autosomal recessive

Charcot-MarieTooth disease in 3 families.

M.A.M. SalihI, E. Mikesova2 , S.A. Elmalik3 , M.M. Kabiraj4, A.E.M. Ahmed5 ,

M.M. MUkhtar6, E. LeGuern2 ,7 and H. Azzedine2

IDivision of Pediatric Neurology, Department Of Pediatrics, College of Medicine,

King Saud University, Riyadh, Saudi Arabia; 'INSERM U679, Hospital de la

Pitie-SalpetIiere, Paris, France; 'Department of

Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia;

4Division of Clinical Neurophysiology, DepaItment of Neuroscience, Armed Forces

Hospital, Riyadh, Saudi Arabia.; 'Department of Physiology, Faculty of Medicine,

University of Khartoum, Sudan.; 'Institute of Endemic Diseases, Faculty of

Medicine, University of Khartoum, Sudan; 'UF de genetique, Depattement de

Genetique et Cytogenetique, Hopital de la Pitie-Salpetriere, Paris, France

We describe 3 consanguinous families with autosomal recessive axonal phenotype

of Charcot-Marie- Tooth disease (ARCMT2). These consisted of 16 individuals aged

2 - 35 years, 5 of them were affected. Onset was about 2 years with delayed

walking, evolving into high steppage gait and distal lower limb muscle weakness

and wasting. Cognitive

development was normal, ambulation was preserved and no scoliosis was detected

in the affected individuals.

Nerve conduction studies were compatible with axonal CMT. However,

nerve pathology showed prominent loss of large myelinated axons and typical

onion bulbs formations. These families were screened for 12 microsatellites

markers covering the 2 more frequent ARCMT210ci (CMT4AJ2K and CMT2Bl).

Assignment of the families to the

CMT4B12K was established by homozygocity mapping and confirmed by linkage

analysis.

Sequencing of GDAP1 was performed in all members of the 3 families and 3 new

mutations were identified. To the best of our knowledge, these are the first

GDAP1 mutations reported in the Arabian Peninsula. The phenotype is of axonal

type and is compatible with the

majority of previously reported cases.