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
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...
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Published in | Molecular neurobiology Vol. 54; no. 4; pp. 2428 - 2434 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.05.2017
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0893-7648 1559-1182 |
DOI: | 10.1007/s12035-016-9800-y |