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The text is the summary of recent articles on lowe syndrome at 75 thresold from National Library of Medicine (NLM). This information is subject to NCBI's Disclaimer and Copyright notice.
(3)c University of North Carolina School of Medicine , Chapel Hill , North Carolina , USA . Nystagmus, optic Atrophy, and strabismus are among the more common, nonspecific, ocular manifestations that contribute to neuro-ophthalmological morbidity . Common dysmorphic oculofacial findings include anophthalmia, microphthalmia, hypertelorism, and abnormalities in the configuration or orientation of the palpebral Fissures . Nearly 200 OCRL mutations related to lowe syndrome have been found worldwide, with only ten mutations among the Chinese population . Mutations in this gene cause lowe syndrome (LS) or type 2 Dent disease, of which low-molecular-weight (LMW) proteinuria is a characteristic feature .
Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract . The current genetic models of congenital cataract include Autosomal Dominant, Autosomal recessive, and sex-linked Inheritance . Sex-linked congenital cataract could be inherited through the X or Y chromosome . Congenital cataract is a Symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-Hünermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome . On the other Hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified .
Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients . In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract . OCRL variants have not only been found in classic lowe syndrome, but also in patients with a predominantly Renal phenotype classified as Dent disease type 2 (Dent-2) . Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are Individual differences in the ability to compensate for the loss of enzyme function . To address this, we determined the glomerular sieving coefficient of renin and prorenin and measured urinary renin/prorenin 1) after inducing prorenin in Cyp1a1-Ren2 rats and 2) in patients with Dent disease or Lowe syndrome, disorders characterized by defective Proximal tubular reabsorption .
They are 10 different isoenzymes and several splice variants in the human genome that are involved in a series of human pathologies such as the lowe syndrome, the Joubert and MORM syndromes, breast cancer, glioblastoma, gastric cancer and several other type of cancers . Inositol 5-phosphatases can be amplified in human cancer Cells, whereas the 3- and 4- phosphatase Tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted . The inositol 5-phosphatases are critically involved in a complex network of higly regulated phosphoinositides, affecting the lipid content of PI(3, 4, 5)P3, PI(4, 5)P2 and PI(3, 4)P2 . OCRL1 5-phosphatase activity, which is membrane curvature sensitive, is stimulated by IPIP27A-mediated engagement of OCRL1 with pacsin 2 and promotes scission of MPR-containing carriers . This lack of homogeneity of clinical manifestations suggests that the difference in phenotypes between the two groups might reflect different pathophysiological mechanisms, probably depending on the diverse genes involved .
In particular in vitro and in vivo evidence demonstrates an important role of OCRL in recycling of megalin, a multi-ligand receptor crucial for reabsorption of nutrients in the proximal tubulus, a process severely impaired in lowe syndrome patients . These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in lowe syndrome and Dent-2 disease . Clinical and laboratory findings of lowe syndrome are well documented . To search for mechanisms linked to clinical variability observed between these two OCRL mutation-associated pathologies, we compared Dermal fibroblasts from independent patients, four affected by Dent-2 disease and six with lowe syndrome . OCRL, an inositol polyphosphate 5-phosphatase, is mutated in lowe syndrome .
Here, we show that TM Cells, which are defective in glaucoma, have primary cilia that are critical for response to pressure changes . Here we show that OCRL loss in Lowe syndrome patient fibroblasts impacts clathrin-mediated endocytosis and results in an endocytic defect . These Cells exhibit an accumulation of clathrin-coated vesicles and an increase in U-shaped clathrin-coated pits, which may result from sequestration of coat components on uncoated Vesicles . FS occurs in rare inherited Renal diseases including cystinosis, Dent disease, lowe syndrome, and Autosomal Dominant FS . The main presentation was congenital cataract in both eyes necessitating early cataract removal in the 11 patients with impaired visual acuity .
OCRL1 contains 24 exons and encodes a 105-kDa phosphatidylinositol (4,5) bisphosphate 5-phosphatase . Impaired inositol polyphosphate-5-phosphatase activity elevates phosphatidylinositol (4,5) bisphosphate levels that are required for vesicle trafficking within the Golgi apparatus, actin cytoskeleton remodeling closely associated with Golgi, and endosomal membrane trafficking . Accordingly, abnormalities in the actin cytoskeleton may influence the function of renal epithelial Cells in patients with lowe syndrome . The morphological exploration was completed by secondary brain abnormalities (periventricular lesions) . OCRL Mutations were not only found in classic lowe syndrome, but also in milder affected patients, classified as having Dent-2 disease .
There is a phenotypic continuum within patients with Dent-2 disease and lowe syndrome, suggesting that there are individual differences in the ability to compensate for loss of enzyme function . However, the mechanisms leading to the clinical manifestations are still poorly understood and we are far from an effective therapy . OCRL1 is the gene responsible for lowe syndrome and encodes an inositol polyphosphate-5-phosphatase . We present an 11-year-old boy with Lowe syndrome, who had a de novo frameshift Mutation in exon 22 that resulted in amino acid substitution and premature codon termination at position 788 .
References: 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ,Press Refresh to fetch fresh content with references from pubmed. This content was cached on 2017-04-21 comments powered by Disqus
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