CMT 4C French Canadians: Founder SH3TC2 mutations responsible

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Neuromuscul Disord. 2008 May 27.

Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians

cluster.

Gosselin I, Thiffault I, Tétreault M, Chau V, Dicaire MJ, Loisel L,

Emond M, Senderek J, Mathieu J, Dupré N, Vanasse M, Puymirat J, Brais

B.

Laboratoire de neurogénétique de la motricité, Centre d'Excellence en

Neuromique de l'Université de Montréal, Centre de Recherche du Centre

Hospitalier de l'Université de Montréal, M4211-L3, Hôpital Notre-Dame-

CHUM, 1560 Sherbrooke East, Montréal, Que., Canada H2L 4M1.

Charcot-Marie-Tooth polyneuropathies (CMT) are clinically and

genetically heterogeneous. We describe a French-Canadian cluster of

17 recessive CMT cases belonging to 10 families with variable early-

onset CMT and scoliosis. The patients demonstrate great intra- and

inter-familial variability.

Linkage analysis confirmed that all families are linked to CMT4C

locus on chromosome 5q32 (multipoint LOD score of 9.06). Haplotype

analysis suggests that two SH3TC2 mutations are present in this

cohort.

The majority of carrier chromosomes, 26 of 34 (76%), carry the

c.2860C-->T mutation. Despite extensive sequencing, the other

mutation is not yet uncovered.

This study demonstrates that the clinical variability observed in

CMT4C is due to other factors than the nature of the mutation and

that further work is needed to better define the SH3TC2 gene to

ensure the identification of all CMT4C mutations.