Phenotypic variability of CMT4C in a French-Canadian kindred.
BACKGROUND
Charcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis.


METHODS
Patients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction.


RESULTS
Six of 10 siblings were clinically symptomatic with supportive electrophysiologic features. The proband presented with regional side-to-side sensorimotor asymmetry, typical pes cavus without obvious scoliosis, and unremarkable plain films of the spine. Affected siblings all share symptoms of foot deformity but have variable onset of neuropathic symptoms, degree of extremity weakness, progression of symptoms, and, most notably, evidence of scoliosis. DNA sequence analysis revealed a novel combination of 2 known recessive mutations, p.R904X and p.R954X, in the SH3TC2 gene.


CONCLUSIONS
A broad spectrum of phenotypes should be considered in the possible diagnosis of CMT4C. The absence of scoliosis or late-onset symptoms should not exclude SH3TC2 from the list of candidate genes under consideration. Age of onset and clinical features were variable and suggest that polygenic factors contribute to the final phenotype.
Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, HSC Room 2H22, 1200 Main Street West, Ontario, Canada, L8N 3Z5.
Talia L
TL
Varley
Division of Neurology, University of Ottawa, Ottawa, Ontario, Canada.
Pierre R
PR
Bourque
Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, HSC Room 2H22, 1200 Main Street West, Ontario, Canada, L8N 3Z5.
Steven K
SK
Baker
D000200:Action Potentials / Q000502:physiology; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D004576:Electromyography; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009431:Neural Conduction / Q000502:physiology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D035781:Siblings
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C488620:SH3TC2 protein, human
5q32; CMT4C; Charcot-Marie-Tooth; French-Canadian; SH3TC2