OCRL Mutations in Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Presentations

Abstract

Purpose: Oculocerebrorenal syndrome of Lowe (Lowe syndrome) is a rare X-linked disorder caused by mutations of the OCRL gene. Congenital cataracts and glaucoma, mental retardation, and kidney dysfunction are characteristics of this syndrome. The purpose of this study is to report clinical findings and novel deletion mutations in OCRL gene in two Lowe syndrome patients.

Methods: Two unrelated boys at Riley Children’s Hospital were diagnosed with Lowe syndrome based on the clinical manifestations. Patient-derived blood cells were extracted for RNA or genomic DNA, which were used as templates for OCRL amplifying and sequencing. Skin biopsy was obtained for cellular analysis. Immunoblotting assay was performed on control and patient fibroblasts with anti-OCRL antibody.

Results: Patient 1 is a 14-day old boy with bilateral nuclear cataracts, corneal edema, and increased intraocular pressure (IOP) of 33 and 28. Low (0.3 mmol/mil/mg protein, normal 2-9) phosphatidylinositol bisphosphate phosphatase and cell growth defects were detected in patient keratinocytes. A novel 4-basepair deletion mutation of gene OCRL (c.739-742delAAAG, p.Lys192Lys fsX8) was identified in exon 8, causing a reading frame shift with unpredicted 8 amino acids.<br /> Patient 2 was diagnosed at 2 months of age with bilateral discoid cataract, corneal edema, and elevated IOP of 40 and 41. Family history is positive for a maternal uncle with congenital cataract, mental retardation, and renal failure. The patient’s mother was also noted to have multiple lenticular fleck opacities. This patient has a novel 37-basepair deletion mutation at the tail of exon 14 of OCRL (c. 1595-1631del, p. Tyr477Leu fsX30), resulting truncated protein with wrongly translated 30 amino acids.

Conclusions: Two novel deletion mutations in OCRL gene were identified in two unrelated patients with congenital cataracts in Lowe syndrome. Both patients underwent cataract and multiple glaucoma surgeries with resulting poor vision.