Human Genome Variation (Jun 2023)

The HCN1 p.Ser399Pro variant causes epileptic encephalopathy with super-refractory status epilepticus

  • Yu Kobayashi,
  • Jun Tohyama,
  • Noriyuki Akasaka,
  • Kei Yamada,
  • Moemi Hojo,
  • Eijun Seki,
  • Masaki Miura,
  • Noriko Soma,
  • Takeshi Ono,
  • Mitsuhiro Kato,
  • Mitsuko Nakashima,
  • Hirotomo Saitsu,
  • Naomichi Matsumoto

DOI
https://doi.org/10.1038/s41439-023-00247-8
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 4

Abstract

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Abstract HCN1 is one of four genes encoding hyperpolarization-activated cyclic nucleotide-gated channels. The phenotypic spectrum associated with HCN1 variants ranges from neonatal developmental and epileptic encephalopathy to idiopathic generalized epilepsy. We report a Japanese patient with repetitive focal seizures and super-refractory status epilepticus since early infancy caused by a de novo HCN1 variant, NM_021072.4, c.1195T>C, p.(Ser399Pro). This variant might have a dominant-negative effect on channel function, leading to severe epileptic encephalopathy.