Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy
Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy
复制标题
DOI：
10.1212/01.wnl.0000238513.70878.54
复制
发表时间：
2006-10-10
期刊：
影响因子：
9.9
通讯作者：
Zara, F.
中科院分区：
文献类型：
--
作者：
Madia, F.;Striano, P.;Zara, F.
目的：鉴定婴儿严重肌阵挛癫痫 (SMEI) 患者中涉及 SCN1A 的隐性染色体缺失。方法：对 39 例无 SCN1A 点突变的 SMEI 患者及其父母进行 14 个基因内 SCN1A 多态性分型，以鉴定半合子。使用包含染色体 2q24.3-q31.1 的基因组克隆通过荧光原位杂交分析确定亲本起源和基因组缺失的程度。通过键入单核苷酸多态性和微卫星标记，可以更精细地绘制删除断点。结果：我们确定了三名 SMEI 患者，他们的 SCN1A 基因座存在基因组缺失。删除大小在 607 kb 到 4.7 Mb 之间。所有受试者的父本染色体缺失均源自从头。一名患者患有中枢性性早熟和腭裂。基因型-表型相关性表明这些临床特征是由 SCN1A 着丝粒基因引起的。结论：缺乏 SCN1A 点突变的婴儿期严重肌阵挛癫痫 (SMEI) 患者应检查是否存在涉及 SCN1A 的隐性染色体缺失。由于连续基因缺失，癫痫以外的临床特征可能与 SMEI 相关。
Objective: To identify cryptic chromosomal deletions involving SCN1A in patients with severe myoclonic epilepsy of infancy (SMEI). Methods: Thirty-nine patients with SMEI and without SCN1A point mutations and their parents were typed with 14 intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and the extent of genomic deletions were determined by fluorescence in situ hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1. Deletion breakpoints were more finely mapped by typing single-nucleotide polymorphisms and microsatellite markers. Results: We identified three patients with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal chromosome in all subjects. One patient had central precocious puberty and palatoschisis. Genotype-phenotype correlations suggest that these clinical features are due to genes centromeric to SCN1A. Conclusions: Patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A. Clinical features other than epilepsy could be associated with SMEI as a consequence of deletions in contiguous genes.