Molecular Neurobiology

, Volume 54, Issue 4, pp 2428–2434

A Point Mutation in SCN1A 5′ Genomic Region Decreases the Promoter Activity and Is Associated with Mild Epilepsy and Seizure Aggravation Induced by Antiepileptic Drug

  • Qu-Wen Gao
  • Li-Dong Hua
  • Jie Wang
  • Cui-Xia Fan
  • Wei-Yi Deng
  • Bin Li
  • Wen-Jun Bian
  • Chuan-Xing Shao
  • Na He
  • Peng Zhou
  • Wei-Ping Liao
  • Yi-Wu Shi
Article

Abstract

The SCN1A gene with 1274 point mutations in the coding regions or genomic rearrangements is the most clinically relevant epilepsy gene. Recent studies have demonstrated that variations in the noncoding regions are potentially associated with epilepsies, but no distinct mutation has been reported. We sequenced the 5′ upstream region of SCN1A in 166 patients with epilepsy and febrile seizures who were negative for point mutations in the coding regions or genomic rearrangements. A heterozygous mutation h1u-1962 T > G was identified in a patient with partial epilepsy and febrile seizures, which was aggravated by oxcarbazepine. This mutation was transmitted from the patient’s asymptomatic mother and not found in the 110 normal controls. h1u-1962 T > G was located upstream the most frequently used noncoding exon and within the promoter sequences. Further experiments showed that this mutation decreased the promoter activity by 42.1 % compared with that of the paired haplotype (P < 0.001). In contrast to the null expression that results in haploinsufficiency and severe phenotype, this mutation caused relatively less impairment, explaining the mild epilepsy with incomplete penetrance. The antiepileptic drug-induced seizure aggravation in this patient suggests clinical attention for mutations or variations in noncoding regions that may affect SCN1A expression.

Keywords

SCN1A Mutation Noncoding regions Promoter Partial epilepsy with febrile seizures plus 

Supplementary material

12035_2016_9800_MOESM1_ESM.docx (17 kb)
Supplementary Table 1(DOCX 16 kb)

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Qu-Wen Gao
    • 1
    • 2
    • 3
  • Li-Dong Hua
    • 1
    • 2
  • Jie Wang
    • 1
    • 2
  • Cui-Xia Fan
    • 1
    • 2
  • Wei-Yi Deng
    • 1
    • 2
  • Bin Li
    • 1
    • 2
  • Wen-Jun Bian
    • 1
    • 2
  • Chuan-Xing Shao
    • 1
    • 2
  • Na He
    • 1
    • 2
  • Peng Zhou
    • 1
    • 2
  • Wei-Ping Liao
    • 1
    • 2
  • Yi-Wu Shi
    • 1
    • 2
  1. 1.Institute of Neuroscience and the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouChina
  2. 2.Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaCollaborative Innovation Center for Neurogenetics and ChannelopathiesGuangzhouChina
  3. 3.Department of EpilepsyGuangzhou General Hospital of Guangzhou Military CommandGuangzhouChina

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