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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BibTeX
@article{cestele2026elicited,
title = {{Elicited Repetitive Daily Blindness Associated With Gain-of-Function SCN1A Variants and Responsiveness to Sodium Channel Blockers}},
author = {Sandrine Cestèle and Alexander James Harper and Sebastian Marra and Nathalie Leroudier and Raffaella Rusconi and Sandra Dhifallah and Iain Horrocks and Fenella Jane Kirkham and Iona Margaret Rose Morgan and Jaspal Singh and Daniel John Stobo and Joseph Symonds and Sameer Zuberi and Massimo Mantegazza and Andreas Brunklaus},
journal = {Neurology Genetics},
year = {2026},
month = nov,
doi = {10.1212/nxg.0000000000200352},
url = {https://hal.science/hal-05848023v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Elicited Repetitive Daily Blindness Associated With Gain-of-Function SCN1A Variants and Responsiveness to Sodium Channel Blockers
AU - Sandrine Cestèle
AU - Alexander James Harper
AU - Sebastian Marra
AU - Nathalie Leroudier
AU - Raffaella Rusconi
AU - Sandra Dhifallah
AU - Iain Horrocks
AU - Fenella Jane Kirkham
AU - Iona Margaret Rose Morgan
AU - Jaspal Singh
AU - Daniel John Stobo
AU - Joseph Symonds
AU - Sameer Zuberi
AU - Massimo Mantegazza
AU - Andreas Brunklaus
PY - 2026
DA - 2026/11/02
JO - Neurology Genetics
DO - 10.1212/nxg.0000000000200352
UR - https://hal.science/hal-05848023v1
AB - 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.
SN - 2376-7839
ER -