Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Department of Medical Genetics, King Fahad General Hospital, Jeddah, Saudi Arabia.
CNS Neurol Disord Drug Targets. 2017;16(9):1010-1017. doi: 10.2174/1871527316666170731103509.
Epilepsy is etiologically and genetically complex neurological disorder affecting millions of people worldwide. Juvenile myoclonic epilepsy (JME) is the most common epilepsy syndrome that starts in the teen age group commonly between ages 12, 18, and lasts till adulthood. One out of fourteen people with epilepsy suffers with JME. Myoclonic seizures and muscle twitching or uncontrolled jerking are the most common type of seizures in the people suffering with JME.
To observe the novel CNVs involved in JME, we investigated a Saudi family with nine siblings including one male and one female affected members. In this study we used high density whole genome Agilent sure print G3 Hmn CGH 2x 400K array-CGH chips. Our results showed CNVs including the amplifications and deletions in different chromosomal regions in the patients as compared to the normal members of the family. Amplifications were observed in the chromosome 22 cytoband 22q11.23 with LDL receptor related protein 5 like (LRP5L), Immunoglobulin Lambda-Like Polypeptide 3 (IGLL3) and crystallin beta B2 pseudogene (CRYBB2P) genes respectively whereas the deletions were observed in the chromosomal regions 4q22.2 with Glutamate receptor, ionotropic, delta 2 (GRID2) as potential gene cytoband 1p31.1 with potential Neuronal Growth Regulator 1 gene (NEGR1) gene in this region and NME/NM23 family member (NME7) gene cytoband 1q24. Moreover, the array CGH resulting in deletions and duplication were also validated by using primer for simple PCR or also by using quantitative real time PCR analysis. We found deletions and duplication in JME patients in our study for the first time in Saudi population.
RESULTS & CONCLUSION: The findings in this study suggest that the array-CGH may be considered as a first line of genetic testing for diagnosis of epilepsy unless strong evidence is presented for a monogenic syndrome. The use of high throughput technique in this study will help to identify novel mechanisms underlying epileptic disorder in order to lower the burden of epilepsy in Saudi Arabia.
癫痫是一种病因和遗传复杂的神经障碍疾病，影响着全球数百万人。青少年肌阵挛癫痫（JME）是最常见的癫痫综合征，通常在 12 至 18 岁之间发病，持续到成年。每 14 名癫痫患者中就有 1 人患有 JME。肌阵挛发作和肌肉抽搐或不受控制的抽搐是 JME 患者最常见的发作类型。
为了观察 JME 中涉及的新型 CNV，我们调查了一个有 9 个兄弟姐妹的沙特家庭，其中包括 1 名男性和 1 名女性患者。在这项研究中，我们使用了高密度全基因组 Agilent sure print G3 Hmn CGH 2x 400K 芯片。我们的结果显示，与家族中的正常成员相比，患者的不同染色体区域存在 CNV 扩增和缺失。在染色体 22 的 22q11.23 带中观察到扩增，分别涉及 LDL 受体相关蛋白 5 样（LRP5L）、免疫球蛋白 lambda 样多肽 3（IGLL3）和晶体蛋白 beta B2 假基因（CRYBB2P）基因，而在染色体 4q22.2 中观察到缺失，在该区域可能有谷氨酸受体、离子型、delta 2（GRID2）基因和潜在基因 1p31.1 区的神经元生长调节因子 1 基因（NEGR1）基因，以及该区域的 NME/NM23 家族成员（NME7）基因。此外，通过使用简单 PCR 的引物或通过使用定量实时 PCR 分析，也验证了阵列 CGH 导致的缺失和重复。我们首次在沙特人群中发现 JME 患者存在缺失和重复。
本研究结果表明，除非有明确的单基因综合征证据，否则阵列-CGH 可作为癫痫诊断的一线遗传检测方法。本研究中使用高通量技术将有助于确定癫痫发病的新机制，以降低沙特阿拉伯的癫痫负担。
