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De novo KCNT 1 mutations in early‐onset epileptic encephalopathy
Author(s) -
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,
Tanaka Fumiaki,
Saitsu Hirotomo,
Matsumoto Naomichi
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13072
Subject(s) - west syndrome , epilepsy , mutation , exome sequencing , epileptic spasms , biology , pediatrics , medicine , genetics , neuroscience , gene
Summary KCNT 1 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 ( EOEE s). We performed KCNT 1 ‐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 EOEE s. We identified nine heterozygous KCNT 1 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%). KCNT 1 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 KCNT 1 mutations is largely restricted to EIMFS .