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Na Luo, Laura Claire Mairs, Xinyao Hu, Matthew J Turner, Daniel E Neely, Dan F Spandau, Yang Sun; Identification of a Novel OCRL Mutation in Oculocerebrorenal Syndrome of Lowe. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6422.
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Oculocerebrorenal syndrome of Lowe (Lowe syndrome) is a rare X-linked recessive disease characterized by congenital cataracts, glaucoma, hypotonia, mental retardation, proximal tubular acidosis, and proteinuria. Lowe syndrome is caused by mutations in the OCRL gene. Here we report a case of a 1-day old male that presented with clinical features of Lowe syndrome, and describe a novel OCRL mutation identified in this patient.
Lowe syndrome was diagnosed based on the clinical manifestations of bilateral congenital glaucoma and cataracts at birth and proteinuria. Nested PCR and sequencing techniques were performed to identify mutation of OCRL gene from cDNA in the patient's cells. A skin biopsy was performed to isolate primary keratinocytes. Cellular and molecular abnormalities of patient's keratinocytes were tested by immunofluorescence and immunoblotting.
The patient presented with cloudy corneas, miotic pupils, discoid cataracts, glaucoma (IOP RE:41 mmHg & LE:55mmHg) and proteinuria. A mutation, c.1661A>C (p.Asp499Ala), localized to exon 20 of the OCRL gene, was identified. Cell growth retardation and shortened cilia were observed in patient’s keratinocytes. And cilia length was rescued by transduction of GFP-WT-OCRL. Immunoblot analysis showed decreased expression of OCRL protein with Asp499Ala mutation.
This study identified a novel mutation in the OCRL gene in a patient with Lowe syndrome with congenital glaucoma and cataracts. The loss function of OCRL affected primary cilia development.
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