Brainstem depolarization-induced lethal apnea associated with gain-of-function SCN1A^L263V is prevented by sodium channel blockade.

ABSTRACT: Apneic events are frightening but largely benign events that often occur in infants. Here, we report apparent life-threatening apneic events in an infant with the homozygous SCN1A^L263V missense mutation, which causes familial hemiplegic migraine type 3 in heterozygous family members, in the absence of epilepsy. Observations consistent with the events in the infant were made in an Scn1a^L263V knock-in mouse model, in which apnea was preceded by a large brainstem DC-shift, indicative of profound brainstem depolarization. The L263V mutation caused gain of Na_V1.1 function effects in transfected HEK293 cells. Sodium channel blockade mitigated the gain-of-function characteristics, rescued lethal apnea in Scn1a^L263V mice, and decreas

SUBMITTER: Jansen NA 

PROVIDER: S-EPMC10998578 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature