Phenotypic variability of CMT4C in a French‐Canadian kindred. Issue 3 (14th May 2015)

• Record Type: Journal Article
• Authors: Varley, Talia L.; Bourque, Pierre R.; Baker, Steven K.
• Is Part Of: Muscle & nerve. Volume 52:Issue 3(2015:Sep.)
• Page Start: 444
• Page End: 449
• Publication Date: 2015-05-14
• Subjects: Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.24640
• Languages: English
• ISSNs: 0148-639X

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="mus24640-sec-0001" sec-type="section"> <title>Introduction</title> <p>Charcot‐Marie‐Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis.</p> </sec> <sec id="mus24640-sec-0002" sec-type="section"> <title>Methods</title> <p>Patients in a French‐Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction.</p> </sec> <sec id="mus24640-sec-0003" sec-type="section"> <title>Results</title> <p>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 <italic>SH3TC2</italic> gene.</p> </sec> <sec id="mus24640-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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 <italic>SH3TC2</italic> 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. <italic>Muscle Nerve</italic> 52:444–449, 2015</p> </sec> </abstract>