Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations
Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations
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DOI：
10.1212/wnl.0b013e3181f4d7bf
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发表时间：
2010-09-01
期刊：
影响因子：
9.9
通讯作者：
De Jonghe, P.
中科院分区：
文献类型：
--
作者：
Deprez, L.;Weckhuysen, S.;De Jonghe, P.
目的：编码syntaxin结合蛋白1的STXBP1杂合突变最近在大田原综合征（一种发病很早的癫痫性脑病）中被发现。为了探索与STXBP1突变相关的表型谱，我们分析了一组不明原因的早发性癫痫性脑病患者。方法：对106例早发性癫痫性脑病患者进行临床分析。STXBP1基因的突变分析采用外显子和内含子-外显子边界序列分析和多重扩增定量检测拷贝数变化。结果：我们在106例患者中的6例中发现了4个截断突变和2个微缺失部分影响STXBP1。预测所有突变都会破坏STXBP1的功能，并且有5个突变被证明是从头发生的。携带突变的患者中没有一人患有大田原综合征。1例患者在发病时被诊断为West综合征，而另外5例患者的初始表型不符合特定的公认癫痫综合征。其中3名患者后来发展为韦斯特综合征。所有患者均有重度至重度智力低下，5例患者出现共济失调或运动障碍。结论：本研究表明STXBP1基因突变并不局限于大原综合征患者，在10%（5/49）不属于大原综合征或西综合征的早发性癫痫性脑病患者中也存在STXBP1基因突变，在典型西综合征患者中很少存在STXBP1基因突变。STXBP1突变分析应考虑在这一具有挑战性的患者组的诊断评估。神经病学(R) 2010；75: 1159 - 1165
Objectives: Heterozygous mutations in STXBP1, encoding the syntaxin binding protein 1, have recently been identified in Ohtahara syndrome, an epileptic encephalopathy with very early onset. In order to explore the phenotypic spectrum associated with STXBP1 mutations, we analyzed a cohort of patients with unexplained early-onset epileptic encephalopathies.Methods: We collected and clinically characterized 106 patients with early-onset epileptic encephalopathies. Mutation analysis of the STXBP1 gene was done using sequence analysis of the exon and intron-exon boundaries and multiplex amplification quantification to detect copy number variations.Results: We identified 4 truncating mutations and 2 microdeletions partially affecting STXBP1 in 6 of the 106 patients. All mutations are predicted to abolish STXBP1 function and 5 mutations were proven to occur de novo. None of the mutation-carrying patients had Ohtahara syndrome. One patient was diagnosed with West syndrome at disease onset, while the initial phenotype of 5 further patients did not fit into a specific recognized epilepsy syndrome. Three of these patients later evolved to West syndrome. All patients had severe to profound mental retardation, and ataxia or dyskinetic movements were present in 5 patients.Conclusion: This study shows that mutations in STXBP1 are not limited to patients with Ohtahara syndrome, but are also present in 10% (5/49) of patients with an early-onset epileptic encephalopathy that does not fit into either Ohtahara or West syndrome and rarely in typical West syndrome. STXBP1 mutational analysis should be considered in the diagnostic evaluation of this challenging group of patients. Neurology (R) 2010; 75: 1159-1165