Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Shaanxi Institute of Pediatric Diseases, Xi'an Children's Hospital, Xi'an, China.
Seizure. 2018 Mar;56:88-91. doi: 10.1016/j.seizure.2018.02.005. Epub 2018 Feb 10.
Paroxysmal kinesigenic dyskinesia (PKD) and epilepsy are thought to have a shared genetic etiology. PRRT2 has been identified as a causative gene of both disorders. In this study, we aim to explore the potential novel causative gene in a PRRT2-negative family with three individuals diagnosed with PKD or genetic epilepsy with febrile seizures plus (GEFS+).
Clinical data were collected from all the affected and unaffected members of a PKD/GEFS+ family. The Brain magnetic resonance imaging and 24 h video-EEG of all three affected members were analyzed. Targeted gene-panel sequencing was used to detect the genetic defect in genomic DNAs of three affected and five normal individuals. Co-segregation analysis of putatively pathogenic mutations with the phenotype was carried out in all the family members alive to examine the inheritance status.
The inheritance model of this pedigree was autosomal dominant. A novel, fully co-segregated mutation (NM_000744: c.979G > A) in CHRNA4 was identified in the family with three individuals diagnosed with PKD or GEFS+.
CHRNA4 may be a novel gene causing of PKD and GEFS+. Our study extends the genotypic-phenotypic spectrum of combined epileptic and dyskinetic syndromes, and provides a genetic linkage between PKD and GEFS+.
阵发性运动诱发性运动障碍（PKD）和癫痫被认为具有共同的遗传病因。PRRT2 已被确定为这两种疾病的致病基因。在这项研究中，我们旨在探索一个 PRRT2 阴性的家族中潜在的新的致病基因，该家族中有 3 名个体被诊断为 PKD 或热性惊厥附加症（GEFS+）遗传性癫痫。
收集了一个 PKD/GEFS+家族中所有受影响和未受影响成员的临床数据。对所有 3 名受影响成员的大脑磁共振成像和 24 小时视频脑电图进行了分析。使用靶向基因panel 测序检测了 3 名受影响者和 5 名正常个体基因组 DNA 中的遗传缺陷。对所有在世的家族成员进行了潜在致病性突变与表型的共分离分析，以检查遗传状态。
该家系的遗传模式为常染色体显性遗传。在一个被诊断为 PKD 或 GEFS+的 3 名个体的家族中发现了 CHRNA4 中的一个新的、完全共分离的突变（NM_000744：c.979G > A）。
CHRNA4 可能是引起 PKD 和 GEFS+的一个新基因。我们的研究扩展了合并癫痫和运动障碍综合征的基因型-表型谱，并为 PKD 和 GEFS+之间提供了遗传联系。
