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.
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.
Isabelle
I
Gosselin
Isabelle
I
Thiffault
Martine
M
Tétreault
Vann
V
Chau
Marie-Josée
MJ
Dicaire
Lina
L
Loisel
Monique
M
Emond
Jan
J
Senderek
Jean
J
Mathieu
Nicolas
N
Dupré
Michel
M
Vanasse
Jack
J
Puymirat
Bernard
B
Brais
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