Lowe syndrome (LS) is a lethal X-linked genetic disorder caused by caused by mutations in OCRL1 gene, which encodes a lipid phosphatase Ocrl1, important for many cellular processes. Our lab identified that lack of Ocrl1 function results in defects in cell spreading, cell migration and primary cilia assembly. Over 200 OCRL1 mutations have been identified in LS, but their specific impact on cellular processes is unknown. The phosphatase domain is a hotspot for disease-causing mutations harboring over 80 unique missense mutations. Our results indicate that different mutations within this domain have different effects on Ocrl1 distribution and on triggering cellular phenotypes. This is the first study to establish the link between genotype and phenotype in Lowe syndrome.
1. Studying the relationship between of genotype and phenotype of Lowe Syndrome patients.
2. Learning the function of different domains of Ocrl1 in different cellular processes.