Elicited Repetitive Daily Blindness Associated With Gain-of-Function SCN1A Variants and Responsiveness to Sodium Channel Blockers
Abstract
Background and Objectives: variants. The proband in each family was commenced on sodium channel blocker medication. We performed functional analysis of the previously reported Q1489H and F1499L variants, including the overall effect in GABAergic neurons. Methods: 1.1 voltage-gated sodium channel with either wild type (WT), Q1489H, or F1499L variants. Results: gene for family 3 (c.4027G > T/p.[A1343S]), 4 (c.5350G > T/p.[V1784F]), 5 (c.5006C > T/p.[A1669F]) and 6 (c.5006C > T/p.[A1669F]). Electrophysiologic testing revealed an overall gain-of-function on Nav1.1-mediated currents for the previously reported variants Q1489H and F1499L when compared with WT, particularly when they were expressed in cortical GABAergic neurons. In silico tools predicted gain-of-function in the 3 novel variants. All 4 probands responded well to treatment with carbamazepine reporting fewer migraines and blindness episodes. Discussion: 1.1 variants. Patients in this report responded to sodium channel blocker medications.
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