1. De novo KCNT1 mutations in early-onset epileptic encephalopathy.
- Author
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Ohba, Chihiro, Kato, Mitsuhiro, Takahashi, Nobuya, Osaka, Hitoshi, Shiihara, Takashi, Tohyama, Jun, Nabatame, Shin, Azuma, Junji, Fujii, Yuji, Hara, Munetsugu, Tsurusawa, Reimi, Inoue, Takahito, Ogata, Reina, Watanabe, Yoriko, Togashi, Noriko, Kodera, Hirofumi, Nakashima, Mitsuko, Tsurusaki, Yoshinori, Miyake, Noriko, and Tanaka, Fumiaki
- Subjects
BRAIN diseases ,GENETIC mutation ,PARTIAL epilepsy ,CHILDHOOD epilepsy ,POTASSIUM ions - Abstract
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 (<1 month) in five patients (5/11, 45.5%) to 1-4 months 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. [ABSTRACT FROM AUTHOR]- Published
- 2015
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