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

ABSTRACT:

Purpose

We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods

We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences of SREBF2 variants on SREBP pathway function.

Results

We

SUBMITTER: Moulton MJ 

PROVIDER: S-EPMC12358889 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature