Phenotypic variability of CMT4C in a French-Canadian kindred
Phenotypic variability of CMT4C in a French-Canadian kindred
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DOI：
10.1002/mus.24640
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发表时间：
2015-09-01
期刊：
影响因子：
3.4
通讯作者：
Baker, Steven K.
中科院分区：
文献类型：
--
作者：
Varley, Talia L.;Bourque, Pierre R.;Baker, Steven K.
charcot - marie - tooth 4C型（CMT4C）是一种常染色体隐性髓鞘异常神经病，以早熟和快速进行性脊柱侧凸为特征。方法对1例法裔加拿大人亲属患者进行临床检查、电生理研究和基因组DNA提取。结果10例兄弟姐妹中6例临床症状明显，电生理特征支持。先证者表现为区域性左右感觉运动不对称，典型的腔型，无明显脊柱侧凸，脊柱平片不显著。受影响的兄弟姐妹都有足部畸形的症状，但有不同的神经病变症状、四肢无力的程度、症状的进展，最明显的是有脊柱侧凸的证据。DNA序列分析揭示了SH3TC2基因中2个已知隐性突变p.R904X和p.R954X的新组合。结论CMT4C的诊断应考虑广谱表型。没有脊柱侧凸或迟发性症状不应将SH3TC2从考虑的候选基因列表中排除。发病年龄和临床特征是可变的，表明多基因因素有助于最终表型。神经科学进展，2015
IntroductionCharcot-Marie-Tooth type 4C (CMT4C) is an autosomal recessive dysmyelinating neuropathy characterized by precocious and rapidly progressive scoliosis.MethodsPatients in a French-Canadian kindred were evaluated with clinical examination, electrophysiologic study, and genomic DNA extraction.ResultsSix 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.ConclusionsA 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. Muscle Nerve 52:444-449, 2015