In clinical studies, this project has identified nonsense mutations in OCRL-1 and helped confirm OCRL-1 as the gene defect in Lowe Syndrome. The specific mutation does not predict the severity of disease. Stereotypy (random, repetitive, purposeless movement) has been shown to be a cardinal feature of the behavioral disturbance in Lowe Syndrome and may be controllable with medication. Prenatal detection of cataracts may not be a reliable diagnostic test for Lowe syndrome. In laboratory studies, a brain-specific exon due to alternative splicing of OCRL-1 was identified in mouse and man. Different patterns of splicing may also be present in other neural precursors. cDNA for the mouse homolog (MUSINOS) of human inositol polyphosphate-5-phosphatase (HUMINOS) has been identified and errors in published sequence identified in critical homology regions. The expression of OCRL-1 in fetal mouse is predominantly in the nervous system, adrenal medulla, and kidney, with lower expression in connective tissue stroma; MUSINOS is expressed more diffusely and at lower levels. Finally, The gene for HUMINOS has been mapped to 1p34.
