Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.

Matthew J MoultonKristhen AtalaYiming ZhengDebdeep DuttaDorothy K GrangeWen-Wen LinDaniel J WegnerJennifer A WambachAngela L DukerMichael B BoberLisa KratzCarol A WiseIla OxendineAnas Khanshournull nullMichael F WanglerShinya YamamotoF Sessions ColeJonathan RiosHugo J Bellen

Published in: Genetics in medicine : official journal of the American College of Medical Genetics (2024)

Taken together, these data reveal a mechanism by which SREBF2 pathogenic variants that disrupt the S1P cleavage motif cause disease via dominant-negative antagonism of S1P, limiting the cleavage of S1P targets, including SREBP1 and SREBP2.

Keyphrases

copy number
dna binding
genome wide
electronic health record
intellectual disability
single cell
big data
dna methylation
transcription factor
gene expression
cerebral ischemia
subarachnoid hemorrhage