Ademuwagun Ibitayo Abigail, Adam Yagoub, Rotimi Solomon Oladapo, Syrbe Steffen, Radtke Maximilian, Hentschel Julia, Lemke Johannes R, Adebiyi Ezekiel
Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria.
Biochemistry Department, Covenant University, Ota, Ogun State, Nigeria.
Epilepsia Open. 2025 Feb;10(1):222-232. doi: 10.1002/epi4.13106. Epub 2024 Nov 21.
Nigeria, along with other Sub-Saharan African countries, bears the highest burden of epilepsy worldwide. This high prevalence is attributed to a combination of factors, including a significant incidence of infectious diseases, perinatal complications, and genetic etiologies. Genetic testing is rarely available and is not typically included in the routine diagnostic work-up for individuals with infantile and childhood epilepsy syndromes in these regions. Exome sequencing (ES) offers a diagnostic yield of 24%-62%, but these figures primarily reflect data from high-income countries (HICs) and may not be applicable to low- and middle-income countries (LMICs). In this study, we employed ES to investigate the genetic basis of early-onset epilepsy in 22 affected children from Nigeria.
The study involved sampling of patients diagnosed with early-onset epilepsy syndromes at the Lagos State University Teaching Hospital (LASUTH) Neurology clinic. Venous blood samples were collected, and genomic DNA was isolated and purified. Molecular analysis included DNA fragmentation, ligation, target enrichment, library preparation, and whole-exome sequencing. Computational analysis involved variant calling, curation, and classification using specialized tools and databases.
Pathogenic variants were identified in 6 out of 22 individuals, equaling a diagnostic yield of 27.3% and comprising variants in BPTF, NAA15, SCN1A, TUBA1A and twice in CACNA1A.
In this study, we present the first exome study on early-onset epilepsy syndromes from West Africa, facilitated by a Nigerian-German research collaboration. Our findings reveal a genetic diagnostic yield comparable to that of HICs. The integration of genomic medicine into epilepsy management in Nigeria holds promising prospects for improving patient care and reducing mortality rates.
This study represents the first published exome findings in Nigerian children with early-onset epilepsy, revealing a genetic diagnosis in 27% of cases. Pathogenic variants were identified in five genes amongst 6 of 22 patients, underscoring the potential of genetic testing to enhance epilepsy management in developing nations like Nigeria.
尼日利亚与撒哈拉以南非洲其他国家一样，是全球癫痫负担最重的地区。这种高患病率归因于多种因素，包括传染病、围产期并发症和遗传病因的高发病率。在这些地区，基因检测很少能获得，并且通常不包括在婴儿和儿童癫痫综合征患者的常规诊断检查中。外显子组测序（ES）的诊断率为24%-62%，但这些数据主要反映的是高收入国家（HICs）的数据，可能不适用于低收入和中等收入国家（LMICs）。在本研究中，我们采用外显子组测序来调查22名来自尼日利亚的患病儿童早发性癫痫的遗传基础。
该研究涉及在拉各斯州立大学教学医院（LASUTH）神经科诊所对诊断为早发性癫痫综合征的患者进行采样。采集静脉血样本，分离并纯化基因组DNA。分子分析包括DNA片段化、连接、目标富集、文库制备和全外显子组测序。计算分析涉及使用专门工具和数据库进行变异检测、整理和分类。
在22名个体中的6名中鉴定出致病变异，诊断率为27.3%，包括BPTF、NAA15、SCN1A、TUBA1A中的变异以及CACNA1A中的变异出现了两次。
在本研究中，我们展示了由尼日利亚-德国研究合作促成的关于西非早发性癫痫综合征的第一项外显子组研究。我们的研究结果显示出与高收入国家相当的基因诊断率。将基因组医学纳入尼日利亚的癫痫管理对改善患者护理和降低死亡率具有广阔前景。
本研究代表了尼日利亚早发性癫痫儿童首次发表的外显子组研究结果，在27%的病例中揭示了基因诊断。在22名患者中的6名中，在五个基因中鉴定出致病变异，强调了基因检测在尼日利亚等发展中国家加强癫痫管理的潜力。
