De novo KCNT1 mutations in early‐onset epileptic encephalopathy |
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| Authors: | Chihiro Ohba Mitsuhiro Kato Nobuya Takahashi Hitoshi Osaka Takashi Shiihara Jun Tohyama Shin Nabatame Junji Azuma Yuji Fujii Munetsugu Hara Reimi Tsurusawa Takahito Inoue Reina Ogata Yoriko Watanabe Noriko Togashi Hirofumi Kodera Mitsuko Nakashima Yoshinori Tsurusaki Noriko Miyake Fumiaki Tanaka Hirotomo Saitsu Naomichi Matsumoto |
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| Affiliation: | 1. Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan;2. Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Yokohama, Japan;3. Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan;4. Division of Neurology, Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan;5. Department of Pediatrics, Jichi Medical School, Shimotsuke, Tochigi, Japan;6. Department of Neurology, Gunma Children's Medical Center, Shibukawa, Japan;7. Department of Pediatrics, Epilepsy Center, Nishi‐Niigata Chuo National Hospital, Niigata, Japan;8. Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan;9. Department of Pediatrics, Hiroshima University Hospital, Hiroshima, Japan;10. Department of Neonatology, Medical Center for Maternal and Child Health, St. Mary's Hospital, Kurume, Japan;11. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan;12. Department of Pediatrics, Fukuoka University Chikushi Hospital, Fukuoka, Japan;13. Department of Pediatric Neurology, Fukuoka Children's Hospital, Fukuoka, Japan;14. Department of Neurology, Miyagi Children's Hospital, Sendai, Japan |
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| 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. |
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| Keywords: |
KCNT1
De novo mutation Epilepsy of infancy with migrating focal seizures Early onset epileptic encephalopathies |
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