De Novo STXBP1 Mutations in Mental Retardation and Nonsyndromic Epilepsy
De Novo STXBP1 Mutations in Mental Retardation and Nonsyndromic Epilepsy
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DOI：
10.1002/ana.21625
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发表时间：
2009-06-01
影响因子：
11.2
通讯作者：
Michaud, Jacques L.
中科院分区：
文献类型：
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作者：
Hamdan, Fadi F.;Piton, Amelie;Michaud, Jacques L.
我们对 95 名特发性精神发育迟滞患者的 SNARE 复合体（STX1A、VAMP2、SNAP25）及其调节蛋白（STXBP1/Munc18-1、SYT1）的编码基因进行了测序，这些蛋白对于神经传递至关重要。我们在两名患有严重精神发育迟滞和非综合征性癫痫的患者中发现了 STXBP1 的从头突变（无义，p.R388X；剪接，c.169+1G>A）。逆转录酶聚合酶链反应和测序表明剪接突变在外显子 3 下游产生了一个终止密码子。在 190 名对照受试者或 142 名自闭症患者中没有发现 STXBP1 的从头突变或有害突变。这些结果表明 STXBP1 破坏与常染色体显性智力低下和非综合征性癫痫有关。
We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2, SNAP25) and their regulatory proteins (STXBP1/Munc18-1, SYT1), which are essential for neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo mutations in STXBP1 (nonsense, p.R388X; splicing, c.169+1G>A) in two patients with severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase chain reaction and sequencing showed that the splicing mutation creates a stop codon downstream of exon-3. No de novo or deleterious Mutations in STXBP1 were found in 190 control subjects, or in 142 autistic patients. These results suggest that STXBP1 disruption is associated with autosomal dominant mental retardation and nonsyndromic epilepsy.