期刊
EPILEPSIA
卷 56, 期 9, 页码 E121-E128出版社
WILEY
DOI: 10.1111/epi.13072
关键词
KCNT1; De novo mutation; Epilepsy of infancy with migrating focal seizures; Early onset epileptic encephalopathies
资金
- Ministry of Health, Labour and Welfare of Japan
- Japan Society for the Promotion of Science [25293085, 25293235, 13313587, 24591500]
- Takeda Science Foundation
- Fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program in the Project for Developing Innovation Systems from the 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 [26860816, 24591500] Funding Source: KAKEN
KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1-targeted next-generation sequencing (207 samples) and/or whole-exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K+ conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1month) in five patients (5/11, 45.5%) to 1-4months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS.
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