Genotype & phenotype in Lowe Syndrome: specific OCRL1 patient mutations differentially impact cellular phenotypes.

ABSTRACT: Lowe Syndrome (LS) is a lethal genetic disorder caused by mutations in the OCRL1 gene which encodes the lipid 5' phosphatase Ocrl1. Patients exhibit a characteristic triad of symptoms including eye, brain and kidney abnormalities with renal failure as the most common cause of premature death. Over 200 OCRL1 mutations have been identified in LS, but their specific impact on cellular processes is unknown. Despite observations of heterogeneity in patient symptom severity, there is little understanding of the correlation between genotype and its impact on phenotype. Here, we show that different mutations had diverse effects on protein localization and on triggering LS cellular phenotypes. In addition, some mutations affecting specific domains imparted unique characteristics to the resulting mu

SUBMITTER: Ramadesikan S 

PROVIDER: S-EPMC8091038 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature