Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency.

ABSTRACT:

Purpose

Variants in NUS1 are associated with a congenital disorder of glycosylation, developmental and epileptic encephalopathies, and are possible contributors to Parkinson disease pathogenesis. How the diverse functions of the NUS1-encoded Nogo B receptor (NgBR) relate to these different phenotypes is largely unknown. We present three patients with de novo heterozygous variants in NUS1 that cause a complex movement disorder, define pathogenic mechanisms in cells and zebrafish, and identify possible therapy.

Methods

Comprehensive functional studies were performed using patient fibroblasts, and a zebrafish model mimicking NUS1 haploinsufficiency.

Results

We show that de novo NUS1 variants reduce NgBR and Niemann-Pick type C2 (NPC2) protein amount, impair dolichol bios

SUBMITTER: Yu SH 

PROVIDER: S-EPMC8263489 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature