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

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<jats:title>Abstract</jats:title><jats:p><jats:italic>HCN1</jats:italic> is one of four genes encoding hyperpolarization-activated cyclic nucleotide-gated channels. The phenotypic spectrum associated with <jats:italic>HCN1</jats:italic> 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 <jats:italic>de novo HCN1</jats:italic> 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.</jats:p>

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