Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia.
Department of Child Neurology, Hedi Chaker Hospital, LR19ES15, University of Sfax, Sfax, Tunisia.
Epilepsia Open. 2024 Oct;9(5):1697-1709. doi: 10.1002/epi4.12848. Epub 2024 Jul 25.
To develop a high-throughput sequencing panel for the diagnosis of developmental and epileptic encephalopathy in Tunisia and to clarify the frequency of disease-causing genes in this region.
We developed a custom panel for next-generation sequencing of the coding sequences of 116 genes in individuals with developmental and epileptic encephalopathy from the Tunisian population. Segregation analyses and in silico studies have been conducted to assess the identified variants' pathogenicity.
We report 12 pathogenic variants in SCN1A, CHD2, CDKL5, SZT2, KCNT1, GNAO1, PCDH19, MECP2, GRIN2A, and SYNGAP1 in patients with developmental and epileptic encephalopathy. Five of these variants are novel: "c.149delA, p.(Asn50MetfsTer26)" in CDKL5; "c.3616C > T, p.(Arg1206Ter)" in SZT2; "c.111_113del, p.(Leu39del)" in GNAO1; "c.1435G>C, p.(Asp479His)" in PCDH19; and "c.2143delC, p.(Arg716GlyfsTer10)" in SYNGAP1. Additionally, for four of our patients, the genetic result facilitated the choice of the appropriate treatment.
This is the first report of a custom gene panel to identify genetic variants implicated in developmental and epileptic encephalopathy in the Tunisian population as well as the North African region (Tunisia, Egypt, Libya, Algeria, Morocco) with a diagnostic rate of 30%. This high-throughput sequencing panel has considerably improved the rate of positive diagnosis of developmental and epileptic encephalopathy in the Tunisian population, which was less than 15% using Sanger sequencing. The benefit of genetic testing in these patients was approved by both physicians and parents.
在突尼斯开发一种高通量测序panel，用于诊断发育性和癫痫性脑病，并阐明该地区致病基因的频率。
我们针对突尼斯人群中发育性和癫痫性脑病患者的 116 个基因的编码序列开发了一个定制的 panel 进行下一代测序。我们进行了分离分析和计算机研究，以评估所鉴定的变体的致病性。
我们报告了 12 种致病性变体在 SCN1A、CHD2、CDKL5、SZT2、KCNT1、GNAO1、PCDH19、MECP2、GRIN2A 和 SYNGAP1 中的致病性变体。其中 5 种为新发现的：CDKL5 中的“c.149delA，p.(Asn50MetfsTer26)”；SZT2 中的“c.3616C > T，p.(Arg1206Ter)”；GNAO1 中的“c.111_113del，p.(Leu39del)”；PCDH19 中的“c.1435G > C，p.(Asp479His)”；以及 SYNGAP1 中的“c.2143delC，p.(Arg716GlyfsTer10)”。此外，对于我们的 4 位患者，基因检测结果有助于选择合适的治疗方法。
这是第一个报告在突尼斯人群中（以及北非地区[突尼斯、埃及、利比亚、阿尔及利亚、摩洛哥]）发现与发育性和癫痫性脑病相关的基因变异的定制基因 panel，诊断率为 30%。与使用 Sanger 测序时不到 15%的阳性诊断率相比，这种高通量测序 panel 大大提高了突尼斯人群中发育性和癫痫性脑病的阳性诊断率。医生和家长都认可了对这些患者进行基因检测的益处。
