New Type 2B Mutations Research - from Belgium

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Abstract from Am J Hum Genet 2003 Jan 21;72(3) [epub ahead of print]

Mutations in the Small GTP-ase Late Endosomal Protein RAB7 Cause

Charcot-Marie-Tooth Type 2B Neuropathy.

Verhoeven K, De Jonghe P, Coen K, Verpoorten N, Auer-Grumbach M, Kwon

JM, Fitz D, Schmedding E, De Vriendt E, s A, Van Gerwen V,

Wagner K, Hartung HP, Timmerman V.

Department of Molecular Genetics, Flanders Interuniversity Institute for

iotechnology, Born-Bunge Foundation, University of Antwerp, Antwerp,

Belgium.

Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by

marked distal muscle weakness and wasting and a high frequency of foot

ulcers, infections, and amputations of the toes because of recurrent

infections. CMT2B maps to chromosome 3q13-q22. We refined the CMT2B

locus to a 2.5-cM region and report two missense mutations (Leu129Phe

and Val162Met) in the small GTP-ase late endosomal protein RAB7 which

causes the CMT2B phenotype in three extended families and in three

patients with a positive family history. The alignment of RAB7 orthologs

shows that both missense mutations target highly conserved amino acid

residues. RAB7 is ubiquitously expressed,

and we found expression in sensory and motor neurons.