Point Nonsense Mutations in BRD2 gene of Juvenile Myoclonic Epilepsy (JME) patients: A study from Dravidian Linguistic Population in South Indian Population

Maniyar Roshan Z; Dosi M.A; Parveen Jahan; B.N. Umarji; Shivannarayan G; Parthasaradhi; G; Syed Muneer

Volume : VII, Issue : VI, June - 2017

Point Nonsense Mutations in BRD2 gene of Juvenile Myoclonic Epilepsy (JME) patients: A study from Dravidian Linguistic Population in South Indian Population

Maniyar Roshan Z, Dosi M. A, Parveen Jahan, B. N. Umarji, Shivannarayan G, Parthasaradhi, G, Syed Muneer

Abstract :

BACKGROUND Juvenile myoclonic epilepsies (JME) are primarily genetic in origin and genetically determined adolescent syndrome among the idiopathic generalized epilepsies (IGE) probably involves multiple genes. Direct sequencing of the BRD2 gene revealed a heterozygous point nonsense mutation (C>T and A>T) in JME patients. Molecular genetic analysis revealed that both were heterozygous for a nonsense mutation in Brodamine containing protein–2 (BRD2) in exon 9 which lead to a definite diagnosis of JME. The genetic background for JME accounts for 5–10% of all form of epilepsy. A non–ion channel gene of the BRD2 protein cause programmed cell death in the developing ain. The JME is estimated around 3 in 10,000 with peak age at 14.5 to 15.5 years that affects both genders. Mutation within exons of a structural gene can alter the functioning of the gene product and cause a dramatic phenotypic change in amino acid sequence. OBJECTIVES 1. To support innovative research, of the highest scientific merit, that has the greatest potential for patient benefit. 2. To identify the mutation of BRD2 gene in nuclear DNA in JME patients METHODS The case–control association study design was utilized to test the potential involvement of BRD2 gene variations in the etiology of JME. We performed molecular screening of BRD2 gene coding sequence for the detection of mutation through genomic PCR amplification and direct sequencing by ABI PRISM® 377 DNA Analyzer. RESULT These nonsense mutations involved exon 9 and most of them are autosomal dominant. Direct sequencing of the BRD2 gene showed a heterozygous nonsense mutation at nucleotides 254 and 896 base pairs of exon 9 in two affected unrelated JME cases. INTERPRETATION & CONCLUSION The exact genetic mechanism of JME is still unknown due its multiple genes involvement. Further Familial and twin studies are required to investigate the involvement of BRD1, BRD2 and BRD3 genes in the genetic susceptibility of JME syndrome in central nervous system.