Subscribe to RSS
Evaluation of DNA damage and mutation screening of exon 26 of SCN1A gene in patients with epilepsy
Received: 04 January 2017
Accepted: 07 November 2017
06 May 2018 (online)
Background Epilepsy is one of the most prevalent neurological disorders. Around 50 million people worldwide suffer from Epilepsy, 85% of them are from the developing countries. It is a most significant as well as common brain disorder worldwide. Sodium channel alpha 1 subunit gene (SCN1A) is most commonly mutated the gene in different forms of epilepsy.
Objective To screen the genomic damage and SCN1A gene mutation in patients with epilepsy.
Methods To screen the genetic instability of SCN1A gene using Buccal micronucleus cytome (BMCyt) assay and molecular analysis with Single Strand Conformation Polymorphism (SSCP) technique was used to observe the variations in SCN1A gene.
Results We found significant differences in buccal cells of patients than controls. So, we can interpret that BMCyt assay would be a minimally invasive biomarker to detect DNA damage and mutation screening in the SCN1A gene with SSCP technique showed no variation in epileptic patients.
Conclusion These data confirmed that there is certainly DNA damage and no mutations in the SCN1A gene; hence the genetic instability has occurred in epileptic patients.
- 1 Fisher RS, Boas WV, Blume W. et al. Epileptic seizures and epilepsy: definitions proposed by the international league against epilepsy (ILAE) and the international bureau for epilepsy (IBE). Epilepsia 46 2005; 470-472
- 2 Singh R, McKinlay Gardner RJ, Crossland KM, Scheffer IE, Berkovic SF. Chromosomal abnormalities and epilepsy: a review for clinicians and gene hunters. Epilepsia 43 2002; 127-140
- 3 Mantegazza M, Catterall WA. Voltage-gated Na+ channels. Epilepsia 51 2010; 9
- 4 Catterall WA. Na+ channels and epilepsy. Epilepsia 51 2010; 59
- 5 Zucca C, Redaelli F, Epifanio R. et al. Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified. Arch Neurol 65 2008; 489-494
- 6 Stafstrom CE. Epilepsy: a review of selected clinical syndromes and advances in basic science. J Cereb Blood Flow Metab 26 2006; 983-1004
- 7 Holland N, Bolognesi C, Kirsch-Volders M. et al. The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the human project perspective on current status and knowledge gaps. Mutat Res Rev Mutat Res 659 2008; 93-108
- 8 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16 1988; 1215
- 9 Abilash VG, Radha S, Marimuthu KM. et al. Clinical, cytogenetic and molecular analysis of androgen insensitivity syndromes from south Indian cohort and detection and in-silico characterization of androgen receptor gene mutations. Clin Chim Acta 453 2016; 123-130
- 10 Melcher Ulrich. Molecular Genetics. 2000
- 11 Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci 86 1989; 2766-2770
- 12 Claes LR, Deprez L, Suls A. et al. The SCN1A variant database: a novel research and diagnostic tool. Hum Mutat 30 2009; 904-920
- 13 Scheffer IE, Berkovic SF. Generalized epilepsy with febrile seizures plus: a genetic disorder with heterogeneous clinical phenotypes. Brain 120 1997; 479-490
- 14 Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 68 2001; 1327-1332
- 15 Martin MS, Dutt K, Papale LA. et al. Altered function of the SCN1A voltage-gated sodium channel leads to γ-aminobutyric acid-ergic (GABAergic) interneuron abnormalities. J Biol Chem 285 2010; 9823-9834
- 16 Harkin LA, McMahon JM, Iona X. et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 130 2007; 843-852
- 17 Marini C, Mei D, Temudo T. et al. Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. Epilepsia 48 2007; 1678-1685
- 18 Mulley JC, Nelson P, Guerrero S. et al. A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A. Neurol 67 2006; 1094-1095
- 19 Depienne C, Arzimanoglou A, Trouillard O. et al. An I. Parental mosaicism can cause recurrent transmission of SCN1A mutations associated with severe myoclonic epilepsy of infancy. Hum Mutat 27 2006; 389
- 20 Gennaro E, Santorelli FM, Bertini E. et al. Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy. Biochem Biophys Res Commun 341 2006; 489-493
- 21 Marini C, Mei D, Helen Cross J, Guerrini R. Mosaic SCN1A mutation in familial severe myoclonic epilepsy of infancy. Epilepsia 47 2006; 1737-1740
- 22 Morimoto M, Mazaki E, Nishimura A. et al. SCN1A mutation mosaicism in a family with severe myoclonic epilepsy in infancy. Epilepsia 47 2006; 1732-1736
- 23 Lossin C. A catalog of SCN1A variants. Brain Dev 28 (31) 2009; 114-130
- 24 Morimoto M, Mazaki E, Nishimura A. et al. Clinical study of catastrophic infantile epilepsy with focal seizures. Pediatr Neurol 27 2002; 369-377
- 25 Sarisjulis N, Gamboni B, Plouin P, Kaminska A, Dulac O. Diagnosing idiopathic/cryptogenic epilepsy syndromes in infancy. Arch Dis Child 82 2000; 226-230
- 26 Dlugos DJ, Scattergood TM, Ferraro TN, Berrettinni WH, Buono RJ. Recruitment rates and fear of phlebotomy in pediatric patients in a genetic study of epilepsy. Epilepsy Behav 6 2005; 444-446
- 27 Thomas P, Holland N, Bolognesi C. et al. Buccal micronucleus cytochrome assay. Nat Protoc 4 2009; 825-837
- 28 Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. J Physiol 588 2010; 1849-1859