title: SCN1A gene sequencing in 46 Turkish epilepsy patients disclosed 12 novel mutations.
abstract: OBJECTIVE
  The SCN1A gene is one of the most commonly mutated human epilepsy genes associated with a spectrum of phenotypes with variable degrees of severity. Despite over 1200 distinct mutations reported, it is still hard to draw clear genotype-phenotype relationships, since genetic and environmental modifiers contribute to the development of a particular disease caused by an SCN1A mutation. We aimed to initiate mutational screening of the SCN1A gene in Turkey and advance further our understanding of the relationship between the SCN1A sequence alterations and disease phenotypes such as GEFS+, DS and related epileptic encephalopathies.
  
  
  METHODS
  Mutational analysis of the SCN1A gene was carried out in 46 patients with DS, late-onset DS, GEFS+ and unspecified EE using either direct Sanger sequencing of the coding regions and exon/intron boundaries or massively parallel sequencing.
  
  
  RESULTS
  Nineteen point mutations, 12 of which were novel were identified, confirming the clinical diagnosis of the patients. Patients with a mutation (either truncating or missense) on linker regions had significantly later disease onset than patients with mutations in homology regions. The presence of SCN1A mutations in two clinically unclassified patients supported the association of SCN1A mutations with a wide range of phenotypes.
  
  
  CONCLUSIONS
  The conventional Sanger sequencing method was successfully initiated for the detection of SCN1A point mutations in Turkey in epilepsy patients. Furthermore, a modified strategy of massively parallel pyro-sequencing was also established as a rapid and effective mutation detection method for large genes as SCN1A.
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey.
authors.forename: Sunay
authors.initials: S
authors.lastname: Usluer
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Salar
authors.affiliation: Department of Child Neurology, Gülhane Military Medical School, Ankara, Turkey.
authors.forename: Mutluay
authors.initials: M
authors.lastname: Arslan
authors.affiliation: Department of Pediatrics, Division of Child Neurology, Dokuz Eylül University School of Medicine, İzmir, Turkey.
authors.forename: Uluç
authors.initials: U
authors.lastname: Yiş
authors.affiliation: Department of Pediatrics, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: Bülent
authors.initials: B
authors.lastname: Kara
authors.affiliation: Department of Neurology, Clinical Neurophysiology and Child Neurology Units, Istanbul University, Istanbul Faculty of Medicine, Istanbul Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Tektürk
authors.affiliation: Department of Neurology, Clinical Neurophysiology and Child Neurology Units, Istanbul University, Istanbul Faculty of Medicine, Istanbul Turkey; Department of Neurology, Istanbul University Epilepsy Center, Istanbul Turkey.
authors.forename: Betül
authors.initials: B
authors.lastname: Baykan
authors.affiliation: Department of Child Neurology, Gülhane Military Medical School, İstanbul, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Meral
authors.affiliation: Department of Child Neurology, Marmara University, Medical Faculty, Istanbul.
authors.forename: Dilşad
authors.initials: D
authors.lastname: Türkdoğan
authors.affiliation: Department of Neurology, Clinical Neurophysiology and Child Neurology Units, Istanbul University, Istanbul Faculty of Medicine, Istanbul Turkey.
authors.forename: Nerses
authors.initials: N
authors.lastname: Bebek
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Yalçın Çapan
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey.
authors.forename: Aslı
authors.initials: A
authors.lastname: Gündoğdu Eken
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey. Electronic address: hande@boun.edu.tr.
authors.forename: S Hande
authors.initials: SH
authors.lastname: Çağlayan
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics; D014421:Turkey
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human
keywords: Dravet syndrome; Epileptic encephalopathy; GEFS+; SCN1A mutation