High frequency of SH3TC2 mutations in Czech HMSN I patients
High frequency of SH3TC2 mutations in Czech HMSN I patients
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DOI：
10.1111/j.1399-0004.2011.01640.x
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发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Seeman, P.
中科院分区：
文献类型：
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作者：
Lassuthova, P.;Mazanec, R.;Seeman, P.
Charcot-Marie-Tooth（CMT）神经病4C型（CMT 4C）是一种常染色体隐性（AR）脱髓鞘神经病，伴有由SH 3 TC 2基因突变引起的早期脊柱畸形。为了确定捷克人群中SH 3 TC 2突变的谱，对60名无关的捷克患者的SH 3 TC 2的整个编码区进行测序。流行的突变被证明是p.Arg954Stop。因此，仅检测了另外412例转诊进行CMT检测的患者是否存在p.Arg954Stop。在60例SH 3 TC 2基因测序的患者中，13例（21.7%）患者检测到至少一种突变，7例（11.6%）患者检测到双等位基因致病突变。在412例p.Arg954Stop检测患者中，8例患者（1.94%）发现突变，6例为纯合子，2例为杂合子。通过测序在其中一名患者中检测到第二种致病突变，但在另一名患者中未检测到。检测到9个新的序列变异。在计算机模拟和对照样品中进一步测试其致病性。SH 3 TC 2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名无关患者中发现了至少一种突变。CMT 4C似乎是最常见的AR CMT类型，也是所有CMT类型中最常见的类型之一。突变p.Arg954Stop在捷克人群中非常普遍。患有脱髓鞘性神经病沿着非显性遗传方式且CMT 1A/易患压迫性麻痹的遗传性神经病阴性的患者应检测是否存在p.Arg954Stop突变或SH 3 TC 2基因中的其他突变。
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.