A de novo missense mutation (p.Ala263Val) in SCN2A was identified in a patient with neonatal-onset seizures and late-onset episodic ataxia, leading to a pronounced gain-of-function.
Case Report (n=1)
A de novo missense mutation (p.Ala263Val) in SCN2A causes a gain-of-function that expands the phenotypic spectrum to include late-onset episodic ataxia, myoclonus, and pain.
BACKGROUND: Inherited and de novo mutations in sodium channel genes underlie a variety of channelopathies. Mutations in SCN2A, encoding the brain sodium channel Na(V)1.2, have previously been reported to be associated with benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy. METHODS: We evaluated the clinical characteristics in a patient with a neonatal-onset complex episodic neurologic phenotype. We screened SCN2A for mutations and carried out in vitro electrophysiologic analyses to study the consequences of the identified mutation. We studied the developmental expression of Na(V)1.2 in cerebellum by immunohistochemical analysis. RESULTS: The patient presented with neonatal-onset seizures and variable episodes of ataxia, myoclonia, headache, and back pain after 18 months of age. The patient carries a de novo missense mutation (p.Ala263Val) in SCN2A, which leads to a pronounced gain-of-function, in particular an increased persistent Na(+) current. Immunohistochemical studies suggest a developmentally increasing expression of Na(V)1.2 in granule cell axons projecting to Purkinje neurons. CONCLUSIONS: These results can explain a neuronal hyperexcitability resulting in seizures and other episodic symptoms extending the spectrum of SCN2A-associated phenotypes. The developmentally increasing expression of Na(V)1.2 in cerebellum may be responsible for the later onset of episodic ataxia.
Liao et al. (Mon,) conducted a case report in Neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain (n=1). SCN2A de novo missense mutation (p.Ala263Val) was evaluated on Clinical characteristics and electrophysiologic consequences of the mutation. A de novo missense mutation (p.Ala263Val) in SCN2A was identified in a patient with neonatal-onset seizures and late-onset episodic ataxia, leading to a pronounced gain-of-function.