Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster.
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.
Gosselin
Isabelle
I
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, Hôpital Notre-Dame-CHUM, Montréal, Que., Canada.
Thiffault
Isabelle
I
Tétreault
Martine
M
Chau
Vann
V
Dicaire
Marie-Josée
MJ
Loisel
Lina
L
Emond
Monique
M
Senderek
Jan
J
Mathieu
Jean
J
Dupré
Nicolas
N
Vanasse
Michel
M
Puymirat
Jack
J
Brais
Bernard
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002170:Canada / Q000453:epidemiology / Q000208:ethnology; D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002895:Chromosomes, Human, Pair 5; D016000:Cluster Analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D044465:White People
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C488620:SH3TC2 protein, human