title: Two novel mutations in SCN1A gene in Iranian patients with epilepsy.
abstract: OBJECTIVE
  Epilepsy as a common chronic neurological disorder is characterized by recurrent unprovoked seizures. Febrile seizures are the most common type of epilepsy in infants and children. Our aim was the molecular analysis of SCN1A gene in affected Iranian patients with GEFS+ and Dravet syndrome diagnosed clinically to explain genotype-phenotype correlation and exact classification.
  
  
  METHODS
  The 34 unrelated Iranian families with epilepsy were selected and screened for SCN1A mutations by MLPA, ARMS, and PCR-RFLP confirmed by direct sequencing.
  
  
  RESULTS
  MLPA analysis showed normal patterns, but direct sequencing revealed that generally 20/34 (0.588) probands have common reported single nucleotide polymorphisms (SNPs) (p.A1067G; rs2298771) with allelic frequency as 0.706/0.294 in patients and 0.515/0.485 in control group, respectively, for A/G. No significant differences between groups were observed. Moreover, four novel allelic variants as missense substitutions included two new sequence variation (p.F412 I, p.Y1274N) and two previously reported mutations (p.R101G, p.S103G) that were detected in 4/34 probands but not in control groups and other healthy normal family members.
  
  
  CONCLUSIONS
  Clinical diagnosis could nearly establish the classification, but mutation screening helps clinicians to confirm their data. We found mutation in four probands and confirmed the net diagnosis. Our data suggest that the clinical symptom variations could be also explained, considering the role of modifier genes such as mitochondrial mutations or other genes responsible for drug metabolism pathways including multiple drug resistance family genes (ABCB1) or MTHFR.
authors.affiliation: National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Ebrahimi
authors.forename: Massoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Seyed Hassan
authors.initials: SH
authors.lastname: Tonekaboni
authors.forename: Mohammd Sadegh
authors.initials: MS
authors.lastname: Fallah Mahboob Passand
authors.forename: Sirous
authors.initials: S
authors.lastname: Zainali
authors.forename: Mehdi
authors.initials: M
authors.lastname: Moghadasi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D007492:Iran; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D003294:Seizures, Febrile / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*
chemical_list: D017931:DNA Primers; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels