Disease relevance of Oculocerebrorenal Syndrome

• The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction [1].
• The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked recessively inherited disease characterized by a severe pleiotropic phenotype including mental retardation, bilateral congenital cataract, and renal Fanconi syndrome [2].
• The role of PTEN (phosphatase and tensin homolog deleted on chromosome ten) in cancer, the impact of the Src homology 2-containing inositol-5-phosphatase phosphatases in acute myeloid leukemia or diabetes, the involvement of myotubularin family members in genetic diseases and the implication of OCRL1 in Lowe syndrome will be emphasized [3].
• This method was used to examine changes in the content of urinary hyaluronic acid and chondroitin sulfates isolated from normal individuals and from patients with Lowe Syndrome, Werner Syndrome, and Hutchinson-Gilford Progeria Syndrome [4].
• We describe a 3-year-old boy with Lowe syndrome who previously underwent bilateral cataract surgery with intraocular lens implantation and strabismus surgery and developed an inferior corneal keloid [5].

High impact information on Oculocerebrorenal Syndrome

• Inositol polyphosphate 5-phosphatases are central to intracellular processes ranging from membrane trafficking to Ca(2+) signaling, and defects in this activity result in the human disease Lowe syndrome [6].
• The central region of synaptojanin defines it as a member of the inositol-5-phosphatase family, which includes the product of the gene that is defective in the oculocerebrorenal syndrome of Lowe [7].
• The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization [8].
• The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase [9].
• At least one instance of recombination was found between the G6PD and the Lowe syndrome loci [10].

Chemical compound and disease context of Oculocerebrorenal Syndrome

• SIP-110 also hydrolyzed PtdIns(3,4,5)P3 to PtdIns(3,4)P2 as did recombinant forms of two other 5-phosphatases designated as inositol polyphosphate-5- phosphatase II, and OCRL (the protein that is mutated in oculocerebrorenal syndrome) [11].
• Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate [12].
• The ratios of Tyr/Cre, Phe/Cre, and Trp/Cre for Lowe syndrome were 0.497, 0.321, and 0.495, respectively [13].
• Urine samples from two patients with the Lowe syndrome were analyzed for sialic acid and mucopolysaccharides [14].
• Two families of Lowe oculocerebrorenal syndrome with elevated serum HDL cholesterol levels and CETP gene mutation [15].

Biological context of Oculocerebrorenal Syndrome

• Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene [16].

Anatomical context of Oculocerebrorenal Syndrome

• As a first step in identifying the link between ocrl1 deficiency and the clinical disorder, we have identified a reproducible cellular abnormality of the actin cytoskeleton in fibroblasts from patients with Lowe syndrome [8].
• The Lowe syndrome protein Ocrl1 is a PIP2 5-phosphatase, primarily localized to the trans-Golgi network (TGN), which 'loss of function' mutations result in PIP2 accumulation in patient's cells [17].
• Cell lines from kidney proximal tubules of a patient with Lowe syndrome and a normal individual were used to study the function of OCRL [12].
• The oculocerebrorenal syndrome of Lowe (OCRL; McKusick 309,000) is a rare X-linked disorder characterized by mental retardation, congenital cataracts, and Fanconi syndrome of the proximal renal tubules [18].

Gene context of Oculocerebrorenal Syndrome

• Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice [1].
• Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network [19].
• At least two instances of recombination between Xg blood-group and Lowe syndrome loci [10].
• Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus [20].
• CONCLUSIONS: Slit-lamp examination is a highly accurate and sensitive test for carrier detection in Lowe syndrome, particularly in women of reproductive age [21].

Analytical, diagnostic and therapeutic context of Oculocerebrorenal Syndrome

• PURPOSE: To further describe the glaucoma with the oculocerebrorenal syndrome of Lowe (OCRL) including the responsible filtration angle abnormalities and response to treatment [22].

References