期刊
NEUROLOGY
卷 81, 期 11, 页码 992-998出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182a43e57
关键词
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资金
- Ministry of Health, Labour and Welfare of Japan [24133701, 11103577, 11103340, 10103235]
- Japan Society for the Promotion of Science [24591500, 10013428, 12020465]
- Takeda Science Foundation
- Japan Science and Technology Agency
- Strategic Research Program for Brain Sciences [11105137]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [12024421]
- Grants-in-Aid for Scientific Research [24118007, 24591500] Funding Source: KAKEN
Objective: We aimed to investigate the possible association between SCN2A mutations and early-onset epileptic encephalopathies (EOEEs). Methods: We recruited a total of 328 patients with EOEE, including 67 patients with Ohtahara syndrome (OS) and 150 with West syndrome. SCN2A mutations were examined using high resolution melt analysis or whole exome sequencing. Results: We found 14 novel SCN2A missense mutations in 15 patients: 9 of 67 OS cases (13.4%), 1 of 150 West syndrome cases (0.67%), and 5 of 111 with unclassified EOEEs (4.5%). Twelve of the 14 mutations were confirmed as de novo, and all mutations were absent in 212 control exomes. A de novo mosaic mutation (c.3976G>C) with a mutant allele frequency of 18% was detected in one patient. One mutation (c.634A>G) was found in transcript variant 3, which is a neonatal isoform. All 9 mutations in patients with OS were located in linker regions between 2 transmembrane segments. In 7 of the 9 patients with OS, EEG findings transitioned from suppression-burst pattern to hypsarrhythmia. All 15 of the patients with novel SCN2A missense mutations had intractable seizures; 3 of them were seizure-free at the last medical examination. All patients showed severe developmental delay. Conclusions: Our study confirmed that SCN2A mutations are an important genetic cause of OS. Given the wide clinical spectrum associated with SCN2A mutations, genetic testing for SCN2A should be considered for children with different epileptic conditions.
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