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De novo KCNT 1 mutations in early‐onset epileptic encephalopathy

2015; Wiley; Volume: 56; Issue: 9 Linguagem: Inglês

10.1111/epi.13072

1528-1167

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,

Genomics and Rare Diseases

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 .