Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi complex. Several mutations were reported in patient's OCRL gene leading to enzyme deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo mutation in exon 10. The patient aged of 19 months was referred to our medical centre because of a psychomotor retardation. He had a medical history of eye abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5 weeks old. Cataract has been treated after chirurgical therapy but ocular hypertonia persisted. Physical examination revealed an axial hypotonia and walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L), a slight decrease of serum phosphate level (24 mg/L) and an increased serum phosphatase activity. Further studies showed mild proteinuria, urinary bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical and biological data, Lowe syndrome has been suggested. In this context, molecular investigation has been performed using dHPLC/sequencing techniques which allow identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10 of the OCRL gene. The mutation was not found in the probant's mother suggesting a neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations have been reported, variations were noted concerning their localization as well as their type. To our knowledge, this is the first report of the neo mutation c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in a Moroccan patient.
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PMID:[Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]. 1642 Sep 90

Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years.
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PMID:Lowe syndrome. 1672 54

A 10-year-old boy presented with a severe and diffuse mosaic skin hypopigmentation running (in narrow bands) along the lines of Blaschko associated with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia, bilateral punctate cataract, microretrognathia, short neck, pectus excavatum, joint hypermobility, mild muscular hypotonia, generalized seizures, and mild mental retardation. Cranial magnetic resonance imaging revealed hypoplastic corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse subcortical, periventricular cystic-like lesions. Similar dysmorphic features were observed in the child's mother, but with no imaging abnormalities. The facial phenotype coupled with the cysts in the brain was strongly reminiscent of the oculocerebrorenal Lowe syndrome. Full chromosome studies in the parents and the proband and mutation analysis on peripheral blood lymphocytes (and on skin cultured fibroblasts from affected and unaffected skin areas in the child) in the genes for subcortical band heterotopia (DCX (Xq22.3-q23)], lissencephaly (PAFAH1B1, alias LIS1, at 17p13.3), and oculocerebrorenal syndrome of Lowe (OCRL at Xq23-q24)] were unrevealing. This constellation of multiple congenital anomalies including skin hypopigmentation and eye, musculoskeletal, and nervous system abnormalities was sufficiently characterized to be regarded as a novel example of pigmentary mosaicism of the Ito type (i.e., hypomelanosis of Ito).
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PMID:Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions. 1938 77

Dent-2 disease and Lowe syndrome are two pathologies caused by mutations in inositol polyphosphate 5-phosphatase OCRL gene. Both conditions share proximal tubulopathy evolving to chronic kidney failure. Lowe syndrome is in addition defined by a bilateral congenital cataract, intellectual disability, and hypotonia. The pathology evolves in two decades to a severe condition with renal complications and a fatal issue. We describe here a proof of principle for a targeted gene therapy on a mutation of the OCRL gene that is associated with Lowe syndrome. The affected patient bears a deep intronic mutation inducing a pseudo-exon inclusion in the mRNA, leading to a OCRL-1 protein loss. An exon-skipping strategy was designed to correct the effect of the mutation in cultured cells. We show that a recombinant U7-modified small RNA efficiently triggered the restoration of normal OCRL expression at mRNA and protein levels in patient's fibroblasts. Moreover, the PI(4,5)P2 accumulation and cellular alterations that are hallmark of OCRL-1 dysfunction were also rescued. Altogether, we provide evidence that the restoration of OCRL-1 protein, even at a reduced level, through RNA-based therapy represents a potential therapeutic approach for patients with OCRL splice mutations.
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PMID:Functional Characterization and Rescue of a Deep Intronic Mutation in OCRL Gene Responsible for Lowe Syndrome. 2779 Jul 96

We describe a boy who presented with neonatal hypotonia, followed by delayed motor development and growth impairment. Further evaluation revealed rickets caused by proximal renal tubular dysfunction. At age 3, the boy exhibited dysmorphic features and bilateral cataract. Genetic analysis of the OCRL gene showed a novel variant in exon 13: c.1250T>A, p.Val417Asp; in silico and segregation analysis confirmed the variant to be pathogenic, compatible with the diagnosis of the oculocerebrorenal syndrome of Lowe. Lowe syndrome is a rare multisystemic disorder; the diagnostic triad requires involvement of the eye, central nervous system and the proximal renal tubule. Typical clinical features are congenital cataract, glaucoma, hypotonia, mental and behavioral problems, benign skin lesions, platelet dysfunction and dental abnormalities. Phenotypic features early in life may be nonspecific, which is illustrated by this case with a late manifestation of cataract. Because an early diagnosis can lead to better counseling and treatment, we suggest urinary testing for proteinuria as a part of the evaluation of children with unexplained hypotonia.
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PMID:Hypotonia and delayed motor development as an early presentation of Lowe syndrome: case report and literature review. 3050 82

Mutations of the inositol 5-phosphatase OCRL cause Lowe syndrome (LS), characterized by congenital cataract, low IQ, and defective kidney proximal tubule resorption. A key subset of LS mutants abolishes OCRL's interactions with endocytic adaptors containing F&H peptide motifs. Converging unbiased methods examining human peptides and the unicellular phagocytic organism Dictyostelium discoideum reveal that, like OCRL, the Dictyostelium OCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). In addition, a novel conserved F&H interactor was identified, GxcU (in Dictyostelium) and the Cdc42-GEF FGD1-related F-actin binding protein (Frabin) (in human cells). Examining these proteins in D. discoideum, we find that, like OCRL, Dd5P4 acts at well-conserved and physically distinct endocytic stations. Dd5P4 functions in coordination with F&H proteins to control membrane deformation at multiple stages of endocytosis and suppresses GxcU-mediated activity during fluid-phase micropinocytosis. We also reveal that OCRL/Dd5P4 acts at the contractile vacuole, an exocytic osmoregulatory organelle. We propose F&H peptide-containing proteins may be key modifiers of LS phenotypes.
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PMID:Lowe syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL in Dictyostelium discoideum. 3121 33