Department of Neurology, Children's Hospital Boston, Boston, Massachusetts 02115, USA.
Epilepsia. 2012 Aug;53(8):e146-50. doi: 10.1111/j.1528-1167.2012.03538.x. Epub 2012 Jun 12.
Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.
婴儿恶性游走性部分性癫痫（MMPEI）是一种早发性癫痫性脑病，其病因知之甚少。我们试图在一名 MMPEI 患儿中找到一种新的病因，该患儿的健康父母是近亲。我们使用 array 比较基因组杂交（CGH）来鉴定全基因组拷贝数变异，并使用长距离聚合酶链反应进一步描绘 CGH 发现的缺失的断点。先证者存在染色体 20p13 的遗传性纯合缺失，破坏了 PLCB1 基因的启动子区域和前三个编码外显子。对其他 MMPEI 病例进行了 PLCB1 类似缺失或突变的筛查，但未发现突变。我们的研究结果表明，PLCβ1 功能丧失是 MMPEI 的一个原因，这与先前在 Plcb1 基因敲除小鼠模型中的研究结果一致，该模型在早期发生癫痫。我们为 MMPEI 的分子机制提供了新的见解，并进一步将 PLCB1 作为严重儿童癫痫的候选基因。这项工作强调了为严重早发性癫痫综合征寻找遗传病因的重要性。
