Modeling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation.

ABSTRACT: The accurate clinical interpretation of human sequence variation is foundational to personalized medicine. This remains a pressing challenge, however, as genome sequencing becomes routine and new functionally undefined variants rapidly accumulate. Here, we describe a platform for the rapid generation, characterization, and interpretation of genomic variants in haploid cells focusing on Niemann-Pick disease type C (NPC) as an example. NPC is a fatal neurodegenerative disorder characterized by a lysosomal accumulation of unesterified cholesterol and glycolipids. In 95% of cases, NPC is caused by mutations in the NPC1 gene, for which more than 200 unique disease-causing variants have been reported to date. Furthermore, the majority of patients with NPC are compound heterozygotes that o

SUBMITTER: Erwood S 

PROVIDER: S-EPMC6886506 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature