Novel Mutation of OCRL1 in Lowe Syndrome

Liu, Ting; Yue, Zhihui; Wang, Haiyan; Tong, Huajuan; Sun, Liangzhong

doi:10.1007/s12098-014-1581-6

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…In the proximal kidney tubules, it transports hydrogen ions to the endosomes and chloride ions outside, which helps to maintain proper pH values . Other members of the renal background hypophosphatemic rickets include Lowe syndrome ( OCRL1 mutation, OMIM #309000), Fanconi renotubular syndrome—FRTS (various genetic backgrounds) and other conditions with kidney tubule defects where excessive loss of minerals occurs …”

Section: Genetically Conditioned Ricketsmentioning

confidence: 99%

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Michałus

Rusińska

2018

Clinical Genetics

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Apart from the classic forms of rickets, there are rare genetic disorders from the group of vitamin D-resistant rickets where the clinical picture is very similar to the classic forms. Diagnosis of genetically conditioned rickets is often delayed. It is very important to know that a disorder of genetic background may be the cause of the failure of classic treatment in patients with rachitic symptoms. In the group of genetically conditioned rickets there are, among others, congenital hypophosphatemic rickets and vitamin D-dependent rickets type I and II. Congenital hypophosphatemic rickets is characterised by bone mineralisation disturbances related to hypophosphatemia secondary to renal loss of phosphates. The term "hypophosphatemic rickets" covers a group of diseases with similar phenotype but with different genotypes, inheritance models and etiopathogeneses. Mutation of at least 10 genes underlying this disease entity has been described. Vitamin D-dependent rickets are caused by defects of vitamin D metabolism. There are 4 forms described in literature that are distinguished by their genetic causes: type 1A (vitamin D-dependent rickets type IA), type 1B (vitamin D-dependent rickets type IB) and type 2A (vitamin D-dependent rickets type 2A), type 2B (vitamin D-dependent rickets type 2B). A detailed family history in combination with a physical examination, biochemistry and X-ray imaging helps in differential diagnostics of rare forms of rickets.

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Section: Genetically Conditioned Ricketsmentioning

confidence: 99%

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Michałus

Rusińska

2018

Clinical Genetics

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“…In addition to deleterious effects on the eyes and kidneys, OCRL presents clinically with neurological problems including intellectual impairment, developmental delays and behavioural problems. This disease is caused by loss of function mutations in the OCRL gene, which encodes a multidomain PIP 5-phosphatase that dephosporylates PI(4,5)P 2 to produce PI4P [125][126][127][128][129][130][131]. OCRL has been localised to endosomes, the Golgi apparatus, the plasma membrane, phagosomes [132] and, importantly in terms of understanding current thinking on the disease mechanism, clathrin-coated vesicles [133].…”

Section: Cns Disorders Caused By Pi4p and Pi(45)p 2 Imbalancesmentioning

confidence: 99%

PIPs in neurological diseases

Waugh

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Phosphoinositide (PIP) lipids regulate many aspects of cell function in the nervous system including receptor signalling, secretion, endocytosis, migration and survival. Levels of PIPs such as PI4P, PI(4,5)P2 and PI(3,4,5)P3 are normally tightly regulated by phosphoinositide kinases and phosphatases. Deregulation of these biochemical pathways leads to lipid imbalances, usually on intracellular endosomal membranes, and these changes have been linked to a number of major neurological diseases including Alzheimer's, Parkinson's, epilepsy, stroke, cancer and a range of rarer inherited disorders including brain overgrowth syndromes, Charcot-Marie-Tooth neuropathies and neurodevelopmental conditions such as Lowe's syndrome. This article analyses recent progress in this area and explains how PIP lipids are involved, to varying degrees, in almost every class of neurological disease. This article is part of a Special Issue entitled Brain Lipids.

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“…Some patients present with only one of these various phenotypes at birth, which may delay the appropriate diagnosis of the disease 10 . The classic triad of congenital cataracts, infantile hypotonia with intellectual disability, and proximal renal tubular dysfunction often does not present until later in life 11, 12 .…”

Section: Introductionmentioning

confidence: 99%

Ocular Pathology of Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Genotype-Phenotype Analysis

Song

Luo

Alvarado

et al. 2017

Sci Rep

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Mutations in the OCRL1 gene result in the oculocerebrorenal syndrome of Lowe, with symptoms including congenital bilateral cataracts, glaucoma, renal failure, and neurological impairments. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P 2 ). We have identified two novel mutations in two unrelated Lowe syndrome patients with congenital glaucoma. Novel deletion mutations are detected at c.739-742delAAAG in Lowe patient 1 and c.1595-1631del in Lowe patient 2. End stage glaucoma in patient 2 resulted in the enucleation of the eye, which on histology demonstrated corneal keloid, fibrous infiltration of the angle, ectropion uvea, retinal gliosis, and retinal ganglion cell loss. We measured OCRL protein levels in patient keratinocytes and found that Lowe 1 patient cells had significantly reduced OCRL protein as compared to the control keratinocytes. Genotype-phenotype correlation of OCRL1 mutations associated with congenital glaucoma revealed clustering of missense and deletion mutations in the 5-phosphatase domain and the RhoGAP-like domain. In conclusion, we report novel OCRL1 mutations in Lowe syndrome patients and the corresponding histopathologic analysis of one patient's ocular pathology.

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Novel Mutation of OCRL1 in Lowe Syndrome

Cited by 5 publications

References 9 publications

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

Rare, genetically conditioned forms of rickets: Differential diagnosis and advances in diagnostics and treatment

PIPs in neurological diseases

Ocular Pathology of Oculocerebrorenal Syndrome of Lowe: Novel Mutations and Genotype-Phenotype Analysis

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