DNA Laboratory, Department of Child Neurology, 2nd Medical School, University Hospital Motol, Prague, Czech Republic.
Clin Genet. 2011 Oct;80(4):334-45. doi: 10.1111/j.1399-0004.2011.01640.x. Epub 2011 Mar 1.
Charcot-Marie-Tooth (CMT) neuropathy type 4C (CMT4C) is an autosomal recessive (AR), demyelinating neuropathy with early spine deformities caused by mutations in the SH3TC2 gene. To determine the spectrum of SH3TC2 mutations in the Czech population, the entire coding region of SH3TC2 was sequenced in 60 unrelated Czech patients. The prevalent mutation was shown to be the p.Arg954Stop. Therefore, 412 additional patients referred for CMT testing were tested for the presence of p.Arg954Stop only. Of 60 patients in whom the SH3TC2 gene was sequenced, at least one mutation was detected in 13 (21.7%) patients and biallelic pathogenic mutations were detected in 7 (11.6%) patients. Of the 412 patients tested for p.Arg954Stop, the mutation was found in 8 patients (1.94%), 6 were homozygous and 2 were heterozygous. The second causative mutation was detected by sequencing in one of the patients but not in the other. Nine novel sequence variants were detected. Their pathogenicity was further tested in silico and in control samples. Mutations in the SH3TC2 gene are a frequent cause of demyelinating hereditary neuropathy among Czech patients. In total, at least one mutation was found in 21 unrelated patients. CMT4C seems to be the most frequent type of AR CMT and one of the most frequent of all CMT types. Mutation p.Arg954Stop is highly prevalent in the Czech population. Patients with demyelinating neuropathy along with non-dominant mode of inheritance and negative for CMT1A/hereditary neuropathy with liability to pressure palsy should be tested for the presence of the p.Arg954Stop mutation or other mutations in the SH3TC2 gene.
施-彭德龙氏遗传性神经病 4C 型（CMT4C）是一种常染色体隐性（AR）脱髓鞘神经病，由 SH3TC2 基因突变引起脊柱早期畸形。为了确定 SH3TC2 基因突变在捷克人群中的谱，对 60 例无血缘关系的捷克患者的 SH3TC2 基因进行了全编码区测序。结果发现最常见的突变为 p.Arg954Stop。因此，仅对 412 例转诊进行 CMT 检测的患者进行了 p.Arg954Stop 存在的检测。在测序的 60 例患者中，13 例（21.7%）患者至少检测到 1 种突变，7 例（11.6%）患者检测到双等位致病性突变。在检测 p.Arg954Stop 的 412 例患者中，8 例（1.94%）患者发现该突变，其中 6 例为纯合子，2 例为杂合子。在其中一位患者中通过测序检测到第二个致病突变，但在另一位患者中未检测到。共检测到 9 种新的序列变异，进一步在体外和对照样本中进行了致病性测试。SH3TC2 基因突变是捷克患者脱髓鞘遗传性神经病的常见原因。总共在 21 例无血缘关系的患者中发现至少 1 种突变。CMT4C 似乎是 AR CMT 中最常见的类型之一，也是所有 CMT 类型中最常见的类型之一。p.Arg954Stop 突变在捷克人群中高度流行。具有脱髓鞘神经病且遗传方式为非显性且 CMT1A/遗传性压力易感性神经病阴性的患者应检测 p.Arg954Stop 突变或 SH3TC2 基因中的其他突变。
