Mutational Analysis of Gene BRD2 in Patients of Juvenile Myoclonic Epilepsy

  • Hidayetullah . Department of Biotechnology, Faculty of Life Sciences and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Balochistan, Pakistan
  • Shakeela Daud Department of Biotechnology, Faculty of Life Sciences and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Balochistan, Pakistan
  • Saba Manzoor Institute of Biochemistry and Biotechnology, University of Veterinary & Animal Sciences, Lahore
  • Adeel Ahmad Lahore General Hospital, Lahore, Pakistan
  • Palwasha Khan Department of Biotechnology, Faculty of Life Sciences and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Balochistan, Pakistan
  • Asma Yousafzai Department of Biotechnology, Faculty of Life Sciences and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Balochistan, Pakistan
  • Nabeela Tariq Department of Zoology, Sardar Bahadur Khan Women's University Quetta
  • Muhammad Luqman Environmental Sciences, University of Veterinary & Animal Sciences, Lahore
  • Gohram Khan Department of Environmental Science, Faculty of Life Sciences and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Balochistan, Pakistan
Keywords: BRD2 gene, Epilepsy, Electroencephalogram (EEG), Juvenile myoclonic epilepsy (JME), Nervous system, Mutation

Abstract

Background: Epilepsy is characterized as third most common chronic brain disorder. It is known as by an enduring tendency to reduce seizures. Juvenile myoclonic epilepsy is the most frequent generalized epilepsy syndrome in adolescents or childhood. Juvenile myoclonic epilepsy based on finding of linkage analysis, is a genetic association study of photo paroxysmal response was carried out focusing on the BRD2 gene and its polymorphism in German population and other world population.

Materials &Method: For this purpose, five epileptic families were identified, Blood samples were collected with two or more epileptic persons from different areas of Balochistan, and DNA was isolated by Inorganic method. Total 5 exons of BRD2 gene, harboring extensively reported mutations, were selected for genotypic analysis. PCR amplification and DNA sequencing of gene BRD2 (Bromodomain Containing Protein 2) was carried out to confirm any genetic variability in patients with familial inheritance in selected families.

Results: During this study four different mutations were identified (c.610+35 insertion, c.145G>T, 146C>G, p.Ala49Cys, p.lys31lys, c.1062 T>C, p.Asn35Asn) in families with myoclonic epilepsy. Two of the variants are silent mutations; one is 1bp insertion in intron-4 while a missense substitution was also identified. The mutation is probably damaging which is confirmed by an online protein prediction tool Polyphen-2 prediction.

Conclusions: It is concluded that highest percentage of Juvenile myoclonic epilepsies (JME) is in consanguineous marriage families. An important factor contributing to high incidence of Juvenile myoclonic epilepsies (JME) is the unawareness among people about the available diagnostic facilities for the prenatal diagnosis in Pakistan. Further studies involving larger number of patients aiming at genetic categorization of these patients may be helpful in better understanding of underlying pathophysiology.

Published
2022-04-30