Guest guest Posted April 27, 2009 Report Share Posted April 27, 2009 CMT 2B New Mutation ANN Seattle Poster Session Monday, April 27, 2009 3:30 PM [iN2-1.001] A New RAB7 Mutation in a Large French Charcot-Marie-Tooth 2B Family Emmanuelle Salort-Campana, Pouget, le Bernard, Marseille, France, Michel R. Magistris, Armand Bottani, Geneva, Switzerland, is Brice, Paris Cedex 13, France, Philippe Latour, Bron Cedex, France OBJECTIVE: To report a new pathogenic RAB7 mutation responsible of CMT2B. BACKGROUND: Charcot-Marie-Tooth (CMT) type 2B is a dominant inherited axonal neuropathy clinically characterised by marked distal weakness, prominent distal sensory loss and high frequency of ulcers, infections and amputations of the toes. Missense mutations of the small GTPase RAB7 have been reported as causative of CMT2B. DESIGN/METHODS: We describe a large French family with the typical clinical features of CMT2B. Clinical, electrophysiological data were collected from 8 affected patients. DNA samples from 9 family members were tested for RAB7 mutation. RESULTS: 8 family members were definitively affected upon clinical or electrophysiological examination. Several affected members revealed pronounced distal muscle weakness and wasting in the lower limbs and prominent distal sensory loss witch were frequently complicated by mild foot ulcers, infections and rare toe amputations. Electroneuromyography was consistent with a chronic axonal neuropathy. Genetic analysis identified a new dominant mutation consisting in a c.475G>A (p.Ala159 Thr) missense mutation in all affected patients. CONCLUSIONS/RELEVANCE: The clinical and electrophysiological data are quite similar to the previous RAB7 reported families. RAB7 gene has to be tested facing an apparently hereditary sensory neuropathy with only mild motor involvement. The Ala159Thr is a new RAB7 missense mutation and only the fifth reported mutation. It is located in the vicinity of 3 previous RAB7 reported mutations, which affect amino-acids 157 to 161 and cluster in a highly conserved region of the protein. This observation confirms the hypothesis that RAB7 is responsible of CMT2B and highlight the functional importance of the region of the protein clustered by the majority of mutations found to date. Quote Link to comment Share on other sites More sharing options...
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