CMT 4C French Canadians: Founder SH3TC2 mutations responsible

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Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians

cluster

Isabelle Gosselina, Isabelle Thiffaulta, e Tétreaulta, Vann

Chauab, Marie-Josée Dicairea, Lina Loisela, Emondb, Jan

Senderekc, Mathieud, Nicolas Duprée, Michel Vanasseb, Jack

Puymiratf, Bernard Braisabd

http://www.nmd-journal.com/article/S0960-8966(08)00101-6/abstract

Abstract

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 & #8594;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.

Keywords: Charcot–Marie–Tooth, CMT4C, SH3TC2, Founder effect, French-

Canadian a 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

b Clinique neuromusculaire, Centre de réadaptation Marie-Enfant,

Hôpital Sainte-e, Montréal, Que., Canada

c Departement of Human Genetics, Aachen University of Technology,

Aachen, Germany

d Clinique des maladies neuromusculaires, Carrefour de la Santé de

Jonquière, Saguenay, Que., Canada

e CHA-Hôpital Enfant-Jésus, Université Laval, Que., Canada

f CHUQ, Université Laval, Que., Canada