487 results match your criteria Oculocerebrorenal Syndrome


Corneal Keloid in Lowe Syndrome.

Ophthalmology 2022 06;129(6):625

Rothschild Foundation Hospital, Ophthalmology Department, Paris, France.

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A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe syndrome.

Biol Open 2022 01 4;11(1). Epub 2022 Feb 4.

Cellular Organization and Signalling, National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bengaluru 560065, India.

Human brain development is a complex process where multiple cellular and developmental events are coordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Read More

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January 2022

[Analysis of OCRL gene variant in a Chinese pedigree affected with Lowe syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jan;39(1):56-59

Dongguan Maternal and Child Health Care Hospital, Dongguan, Guangdong 523120, China.

Objective: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome.

Methods: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree.

Results: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. Read More

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January 2022

SdhA blocks disruption of the Legionella-containing vacuole by hijacking the OCRL phosphatase.

Cell Rep 2021 11;37(5):109894

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address:

Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. Read More

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November 2021

Genotype Phenotype Correlation in Dent Disease 2 and Review of the Literature: Gene Pleiotropism or Extreme Phenotypic Variability of Lowe Syndrome?

Genes (Basel) 2021 10 11;12(10). Epub 2021 Oct 11.

Kidney Histomorphology and Molecular Biology Laboratory, Nephrology, Dialysis and Transplantation Unit, Department of Medicine-DIMED, University of Padua, 35128 Padua, Italy.

Dent disease is a rare X-linked renal tubulopathy due to and (DD2) mutations. mutations also cause Lowe syndrome (LS) involving the eyes, brain and kidney. DD2 is frequently described as a mild form of LS because some patients may present with extra-renal symptoms (ESs). Read More

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October 2021

IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule.

Hum Mol Genet 2022 04;31(8):1183-1196

Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, The Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.

Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. Read More

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Identification of novel OCRL isoforms associated with phenotypic differences between Dent disease-2 and Lowe syndrome.

Nephrol Dial Transplant 2022 01;37(2):262-270

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1-7 lead to Dent disease-2, whereas those in exons 8-24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms. Read More

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January 2022

Novel pathogenic OCRL mutations and genotype-phenotype analysis of Chinese children affected by oculocerebrorenal syndrome: two cases and a literature review.

BMC Med Genomics 2021 09 6;14(1):219. Epub 2021 Sep 6.

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095, Jiefang Ave., Wuhan, 430030, People's Republic of China.

Background: Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is caused by a mutation of OCRL gene (located at chromosome Xq26.1), which encodes an inositol polyphosphate 5-phosphatase. Read More

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September 2021

Case Report: Corneal Leucoma as a Novel Clinical Presentation of Nail-Patella Syndrome in a 5-Year-Old Girl.

Front Pediatr 2021 14;9:638630. Epub 2021 Jun 14.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Nail-patella syndrome (NPS) is a rare autosomal-dominant disorder characterized by the classic tetrad of absent or hypoplastic finger and toe nails, absent or hypoplastic patella, skeletal deformities involving the elbow joints, and iliac horns. This disease is caused by heterozygous pathogenic variations in the gene, which encodes the LIM homeodomain transcription factor protein (LMX1B). We report a case of corneal leucoma and dysplasia prior to overt steroid-resistant nephrotic syndrome (SRNS) in a patient with NPS. Read More

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A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy.

Int J Mol Sci 2021 May 19;22(10). Epub 2021 May 19.

Department of Biomedical Science, Centre of Membrane Interactions and Dynamics, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.

Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in vitro models for Lowe syndrome/Dent II disease to study the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Read More

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Lysosome positioning and mTOR activity in Lowe syndrome.

EMBO Rep 2021 07 27;22(7):e53232. Epub 2021 May 27.

Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

Lowe syndrome is a rare, developmental disorder caused by mutations in the phosphatase, OCRL. A study in this issue of EMBO Reports shows that OCRL is required for microtubule nucleation and that mutations in this protein lead to an inability to activate mTORC1 signaling and consequent cell proliferation in the presence of nutrients. These defects are the result of impaired microtubule-dependent lysosomal trafficking to the cell periphery and are independent of OCRL phosphatase activity. Read More

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OCRL regulates lysosome positioning and mTORC1 activity through SSX2IP-mediated microtubule anchoring.

EMBO Rep 2021 07 13;22(7):e52173. Epub 2021 May 13.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Lysosomal positioning and mTOR (mammalian target of rapamycin) signaling coordinate cellular responses to nutrient levels. Inadequate nutrient sensing can result in growth delays, a hallmark of Lowe syndrome. OCRL mutations cause Lowe syndrome, but the role of OCRL in nutrient sensing is unknown. Read More

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Establishment of a human induced pluripotent stem cell line (WMUi031-A) from a Lowe syndrome patient carrying a OCRL gene mutation (c.2626dupA).

Stem Cell Res 2021 05 17;53:102294. Epub 2021 Mar 17.

Center of Scientific Research, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Department of Pediatric Endocrine Genetics and Metabolism, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Lowe Syndrome (LS) is a rare X-linked multisystemic disorder syndrome, which can be caused by the gene mutations of OCRL. In present study, the urine cells (UCs) derived from a 12-year-old male LS patient with the hemizygote OCRL gene mutation p.M876N (c. Read More

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Genotype and phenotype studies of Lowe syndrome in three families in Taiwan.

Pediatr Neonatol 2021 05 6;62(3):327-328. Epub 2021 Feb 6.

Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.

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Establishment of patient-specific induced pluripotent stem cell line SDUBMSi009-A from a patient with X-linked Lowe syndrome.

Stem Cell Res 2021 03 13;51:102171. Epub 2021 Jan 13.

Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

X-linked Lowe syndrome is a multisystem disorder showing major abnormalities in the eyes, kidneys and central nervous system. OCRL gene, which encodes an inositol polyphosphate 5-phosphatase, is associated with Lowe syndrome when mutated. Here we report the establishment of SDUBMSi009-A, an induced pluripotent stem cell line derived from patient carrying splicing variant (c. Read More

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Role of oculocerebrorenal syndrome of Lowe (OCRL) protein in megakaryocyte maturation, platelet production and functions: a study in patients with Lowe syndrome.

Br J Haematol 2021 03 2;192(5):909-921. Epub 2021 Feb 2.

Université de Paris, Innovations Thérapeutiques en Hémostase, Paris, INSERM U1140, France.

Lowe syndrome (LS) is an oculocerebrorenal syndrome of Lowe (OCRL1) genetic disorder resulting in a defect of the OCRL protein, a phosphatidylinositol-4,5-bisphosphate 5-phosphatase containing various domains including a Rho GTPase-activating protein (RhoGAP) homology domain catalytically inactive. We previously reported surgery-associated bleeding in patients with LS, suggestive of platelet dysfunction, accompanied with a mild thrombocytopenia in several patients. To decipher the role of OCRL in platelet functions and in megakaryocyte (MK) maturation, we conducted a case-control study on 15 patients with LS (NCT01314560). Read More

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Genotype & phenotype in Lowe Syndrome: specific OCRL1 patient mutations differentially impact cellular phenotypes.

Hum Mol Genet 2021 04;30(3-4):198-212

Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

Lowe Syndrome (LS) is a lethal genetic disorder caused by mutations in the OCRL1 gene which encodes the lipid 5' phosphatase Ocrl1. Patients exhibit a characteristic triad of symptoms including eye, brain and kidney abnormalities with renal failure as the most common cause of premature death. Over 200 OCRL1 mutations have been identified in LS, but their specific impact on cellular processes is unknown. Read More

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Two new missense mutations in the protein interaction ASH domain of OCRL1 identified in patients with Lowe syndrome.

Intractable Rare Dis Res 2020 Nov;9(4):222-228

Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.

The oculocerebrorenal syndrome of Lowe is a rare X-linked disease characterized by congenital cataracts, proximal renal tubulopathy, muscular hypotonia and mental impairment. This disease is caused by mutations in the gene encoding membrane bound inositol polyphosphate 5-phosphatase OCRL1. Here, we examined the gene of two Lowe syndrome patients and report two new missense mutations that affect the ASH domain involved in protein-protein interactions. Read More

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November 2020

The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease.

Kidney Int 2020 10 9;98(4):883-896. Epub 2020 Sep 9.

Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK. Electronic address:

Loss-of-function mutations in the OCRL gene, which encodes the phosphatidylinositol [PI] 4,5-bisphosphate [PI(4,5)P] 5-phosphatase OCRL, cause defective endocytosis and proximal tubule dysfunction in Lowe syndrome and Dent disease 2. The defect is due to increased levels of PI(4,5)P and aberrant actin polymerization, blocking endosomal trafficking. PI 3-phosphate [PI(3)P] has been recently identified as a coactivator with PI(4,5)P in the actin pathway. Read More

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October 2020

Genomic Sequencing for Newborn Screening: Results of the NC NEXUS Project.

Am J Hum Genet 2020 10 26;107(4):596-611. Epub 2020 Aug 26.

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Newborn screening (NBS) was established as a public health program in the 1960s and is crucial for facilitating detection of certain medical conditions in which early intervention can prevent serious, life-threatening health problems. Genomic sequencing can potentially expand the screening for rare hereditary disorders, but many questions surround its possible use for this purpose. We examined the use of exome sequencing (ES) for NBS in the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) project, comparing the yield from ES used in a screening versus a diagnostic context. Read More

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October 2020

RT-PCR analysis of mRNA revealed the splice-altering effect of rare intronic variants in monogenic disorders.

Ann Hum Genet 2020 11 10;84(6):456-462. Epub 2020 Aug 10.

Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai, China.

Background: Variants perturbing the normal splicing of pre-mRNA can lead to human diseases. The splice-altering effect and eventual consequence on gene function was sometimes uncertain and hinders a definitive molecular diagnosis.

Methods: The impact of four rare intronic variants on splicing was analyzed through reverse transcription - polymerase chain reaction (RT-PCR) analysis of mRNA derived from the peripheral blood of patients. Read More

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November 2020

Lowe syndrome - Old and new evidence of secondary mitochondrial dysfunction.

Eur J Med Genet 2020 Oct 23;63(10):104022. Epub 2020 Jul 23.

Laboratory for Advanced Genomics, Ruđer Bošković Institute, Zagreb, Croatia.

The oculocerebrorenal syndrome of Lowe (LS) is a rare, progressive, multisystemic X-linked disorder caused by mutations in OCRL gene. Patients classically present with ocular abnormalities including bilateral congenital cataracts and glaucoma, intellectual delay, severe generalized hypotonia with absent tendon reflexes, and proximal renal tubular dysfunction. Congenital bilateral cataracts and hypotonia are present at birth in almost all patients, while other classical symptoms develop gradually with variable severity. Read More

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October 2020

Onset mechanism of a female patient with Dent disease 2.

Clin Exp Nephrol 2020 Oct 14;24(10):946-954. Epub 2020 Jul 14.

Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, 060-8638, Japan.

Background: Approximately 15% of patients with Dent disease have pathogenic variants in the OCRL gene on Xq25-26, a condition that is referred to as Dent disease 2 (Dent-2). Dent-2 patients sometimes show mild extrarenal features of Lowe syndrome, such as mild mental retardation, suggesting that Dent-2 represents a mild form of Lowe syndrome. To date, eight female patients with Lowe syndrome have been reported, but no female Dent-2 patients have been reported. Read More

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October 2020

Incomplete cryptic splicing by an intronic mutation of OCRL in patients with partial phenotypes of Lowe syndrome.

J Hum Genet 2020 Oct 19;65(10):831-839. Epub 2020 May 19.

Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Mutations of OCRL cause Lowe syndrome, which is characterised by congenital cataracts, infantile hypotonia with mental retardation, and renal tubular dysfunction and Dent-2 disease, which only affects the kidney. While few patients with an intermediate phenotype between these diseases have been reported, the mechanism underlying variability in the phenotype is unclear. We identified an intronic mutation, c. Read More

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October 2020

Identification and functional characterization of a hemizygous novel intronic variant in OCRL gene causes Lowe syndrome.

Clin Exp Nephrol 2020 Aug 11;24(8):657-665. Epub 2020 May 11.

Department of Cell Biology and Medical Genetics, School of Medicine, Zhejiang University, Research Building A713, Yuhangtang Road 866, Hangzhou, China.

Background: Lowe syndrome is an X-linked multisystem disorder affecting eyes, nervous system, and kidney. The main causes are mutations in the OCRL gene that encodes a member of the inositol polyphosphate-5-phosphatase protein family. In this study, we aimed to gain new insights into the consequences of a novel OCRL intronic variant on pre-mRNA splicing as a main cause of Lowe syndrome in a boy. Read More

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Transcriptome analysis of neural progenitor cells derived from Lowe syndrome induced pluripotent stem cells: identification of candidate genes for the neurodevelopmental and eye manifestations.

J Neurodev Disord 2020 05 11;12(1):14. Epub 2020 May 11.

Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.

Background: Lowe syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL, which codes for an inositol polyphosphate 5-phosphatase that plays a key role in endosome recycling, clathrin-coated pit formation, and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. Read More

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Lowe syndrome patient cells display mTOR- and RhoGTPase-dependent phenotypes alleviated by rapamycin and statins.

Hum Mol Genet 2020 06;29(10):1700-1715

Department of Biological Sciences, Purdue University, Hansen Life Sciences Building, Room 321, 201 S. University street, West Lafayette, IN 47907, USA.

Lowe syndrome (LS) is an X-linked developmental disease characterized by cognitive deficiencies, bilateral congenital cataracts and renal dysfunction. Unfortunately, this disease leads to the early death of affected children often due to kidney failure. Although this condition was first described in the early 1950s and the affected gene (OCRL1) was identified in the early 1990s, its pathophysiological mechanism is not fully understood and there is no LS-specific cure available to patients. Read More

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Oculocerebrorenal syndrome of Lowe: Survey of ophthalmic presentations and management.

Eur J Ophthalmol 2020 Sep 27;30(5):966-973. Epub 2020 Apr 27.

Department of Ophthalmology, School of Medicine, Stanford University, Palo Alto, CA, USA.

Background: Lowe syndrome is a rare X-linked disease that is characterized by renal dysfunction, developmental delays, congenital cataracts and glaucoma. Mutations in the oculocerebral renal syndrome of Lowe () gene are found in Lowe syndrome patients. Although loss of vision is a major concern for families and physicians who take care of Lowe syndrome children, definitive cause of visual loss is still unclear. Read More

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September 2020

Angiosarcoma of an Arteriovenous Fistula for Hemodialysis in a Kidney Transplant Recipient Affected by Lowe's Syndrome.

Case Rep Nephrol 2020 13;2020:9734635. Epub 2020 Apr 13.

Università Cattolica del Sacro Cuore, Rome, Italy.

. To describe an uncommon, life-threatening condition such as angiosarcoma of a fistula for hemodialysis occurring in a transplant recipient affected by Lowe's syndrome. . Read More

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Lowe syndrome - Case report with a novel mutation in the oculocerebrorenal gene.

Saudi J Kidney Dis Transpl 2020 Jan-Feb;31(1):285-288

Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India.

The oculocerebrorenal (OCRL) syndrome, also known as Lowe syndrome (LS), is an X-linked recessive disorder that predominantly affects males and is characterized by growth and mental retardation, congenital cataract and renal Fanconi syndrome. OCRL1 is the gene responsible for LS and encodes an inositol polyphosphate-5-phosphatase. We report a male child from North India, with LS with missense mutation in exon 14 of the OCRL gene. Read More

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January 2021