Lyahyai Jaber, Ouled Amar Bencheikh Bouchra, Elalaoui Siham C, Mansouri Maria, Boualla Lamia, DIonne-Laporte Alexandre, Spiegelman Dan, Dion Patrick A, Cossette Patrick, Rouleau Guy A, Sefiani Abdelaziz
Centre de Génomique Humaine, Faculté de Médecine et Pharmacie, Mohammed V University in Rabat, Rabat, Morocco.
Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
BMC Pediatr. 2018 Feb 27;18(1):90. doi: 10.1186/s12887-018-1063-5.
Epilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Epilepsies have a highly heterogeneous background with a strong genetic contribution and various mode of inheritance. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy. The variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the causal genetic mutation, making diagnosis, genetic counseling and treatment decisions difficult. We report the description of a Moroccan family referred to our genetic department with X-linked epileptic seizures as the only initial diagnosis.
Knowing the new contribution of Next-Generation Sequencing (NGS) for clinical investigation, and given the heterogeneity of this group of disorders we performed a Whole-Exome Sequencing (WES) analysis and co-segregation study in several members of this large family. We detected a novel pathogenic PLP1 missense mutation c.251C > A (p.Ala84Asp) allowing us to make a diagnosis of Pelizaeus-Merzbacher Disease for this family.
This report extends the spectrum of PLP1 mutations and highlights the diagnostic utility of NGS to investigate this group of heterogeneous disorders.
癫痫是一组常见且多样的慢性神经系统疾病，其特征为自发、无端且反复发作的癫痫发作。癫痫具有高度异质性背景，有很强的遗传因素及多种遗传模式。X连锁癫痫通常表现为综合征或癫痫性脑病的一部分。X连锁癫痫临床表现的变异性可能归因于多种因素，包括致病基因突变，这使得诊断、遗传咨询及治疗决策变得困难。我们报告了一个摩洛哥家庭的情况，该家庭最初仅诊断为X连锁癫痫发作，后来转诊至我们的遗传科。
鉴于新一代测序（NGS）对临床研究的新贡献，以及这类疾病的异质性，我们对这个大家庭的几名成员进行了全外显子组测序（WES）分析和共分离研究。我们检测到一个新的致病性PLP1错义突变c.251C＞A（p.Ala84Asp），据此我们为这个家庭诊断出佩利措伊斯-梅茨巴赫病。
本报告扩展了PLP1突变谱，并突出了NGS在研究这类异质性疾病方面的诊断效用。
