Zaganas Ioannis, Vorgia Pelagia, Spilioti Martha, Mathioudakis Lambros, Raissaki Maria, Ilia Stavroula, Giorgi Melpomeni, Skoula Irene, Chinitrakis Georgios, Michaelidou Kleita, Paraskevoulakos Evangelos, Grafakou Olga, Kariniotaki Chariklia, Psyllou Thekla, Zafeiris Spiros, Tzardi Maria, Briassoulis George, Dinopoulos Argirios, Mitsias Panayiotis, Evangeliou Athanasios
Neurogenetics Laboratory, Medical School, University of Crete, Heraklion, Crete, Greece.
Neurology Department, University Hospital of Heraklion, Crete, Greece.
Epilepsy Behav Rep. 2021 Aug 27;16:100477. doi: 10.1016/j.ebr.2021.100477. eCollection 2021.
We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5 years, range 2-18 years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu variant. A patient affected with Lafora disease carried the homozygous p.Arg171His variant. A heterozygous variant in the gene (p.Pro282Thr) was found in one patient and a pathogenic variant in the gene (p.Gly820Val) in another patient. Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter gene variant in one patient. In two additional epilepsy patients, the p.Ala1662Val and the novel non-sense p.Phe1330Ter gene variants were found. Finally, in 3 patients we observed a novel heterozygous missense variant in (p.Ala1874Thr), a heterozygous splice site variant in (c.517-2A>G), as a cause of Glut1 deficiency syndrome, and a pathogenic variant in (p.Arg292Leu), respectively. In half of our cases (patients with variants in the , , and genes), a genetic cause with potential management implications was identified.
我们描述了一组10名无亲缘关系的希腊患者（4名女性，6名男性；中位年龄6.5岁，范围2 - 18岁），他们患有具有遗传基础的异质性癫痫综合征。通过全外显子组测序，在这些患者的9个已知癫痫相关基因中鉴定出了致病基因变异，包括两个新的变异。一名患有甘氨酸脑病的患者是p.Arg222Cys和p.Ser77Leu变异的复合杂合子。一名患有拉福拉病的患者携带纯合的p.Arg171His变异。在一名患者中发现了该基因的杂合变异（p.Pro282Thr），在另一名患者中发现了该基因的致病变异（p.Gly820Val）。一名患者的婴儿期发作性乳酸酸中毒伴癫痫与p.Arg446Ter基因变异有关。在另外两名癫痫患者中，发现了p.Ala1662Val和新的无义p.Phe1330Ter基因变异。最后，在3名患者中，我们分别观察到了（p.Ala1874Thr）中的一种新的杂合错义变异、（c.517 - 2A>G）中的一种杂合剪接位点变异（作为Glut1缺乏综合征的病因）以及（p.Arg292Leu）中的一种致病变异。在我们一半的病例（、、和基因有变异的患者）中，确定了具有潜在管理意义的遗传病因。
