466 results match your criteria Oculocerebrorenal Syndrome


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 Mar 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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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

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

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

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

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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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

Insights into the Effect of Lowe Syndrome-Causing Mutation p.Asn591Lys of OCRL-1 through Protein-Protein Interaction Networks and Molecular Dynamics Simulations.

J Chem Inf Model 2020 02 30;60(2):1019-1027. Epub 2020 Jan 30.

Programa de Biologı́a, Facultad de Ciencias Exactas y Naturales , Universidad de Cartagena , Cartagena de Indias , Colombia.

Inositol polyphosphate 5-phosphatase (OCRL-1) participates in the regulation of multiple cellular processes, through the conversion of phosphatidylinositol 4,5-phosphate to phosphatidylinositol 4-phosphate. Mutations in this protein are related to Lowe syndrome (LS) and Dent-2 disease. In this study, the impact of Lowe syndrome mutations on the interactions of OCRL-1 with other proteins was evaluated through bioinformatic and computational approaches. Read More

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February 2020

[Clinical and genetic analysis of an infant with Lowe syndrome caused by exonic duplication of OCRL gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jan;37(1):28-32

Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China.

Objective: To explore the genetic basis of an infant featuring congenital cataract, developmental delay and proteinuria.

Methods: Clinical data and peripheral blood samples of the family were collected. Potential variants were screened by using targeted capture and high-throughput sequencing on a NextSeq 500 platform. Read More

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January 2020

A role for OCRL in glomerular function and disease.

Pediatr Nephrol 2020 04 6;35(4):641-648. Epub 2019 Dec 6.

Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester, M13 9PT, UK.

Background: Lowe syndrome and Dent-2 disease are caused by mutations in the OCRL gene, which encodes for an inositol 5-phosphatase. The renal phenotype associated with OCRL mutations typically comprises a selective proximal tubulopathy, which can manifest as Fanconi syndrome in the most extreme cases.

Methods: Here, we report a 12-year-old male with nephrotic-range proteinuria and focal segmental glomerulosclerosis on renal biopsy. Read More

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Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase.

CEN Case Rep 2020 05 9;9(2):95-100. Epub 2019 Nov 9.

Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh City, Osaka, 562-8562, Japan.

The oculocerebrorenal disorder of Lowe syndrome is an X-linked mutation in the gene oculocerebrorenal syndrome of Lowe 1 (OCRL), characterized by the triad of congenital cataracts, severe intellectual impairment, and renal tubular dysfunction. Manifestations of phenotype in female carriers and patients are extremely rare. We present a female case with congenital cataracts, severe intellectual impairment, sensorineural hearing loss, and renal tubular dysfunction as Lowe syndrome. Read More

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Phosphoinositides in autophagy: current roles and future insights.

FEBS J 2020 01 21;287(2):222-238. Epub 2019 Nov 21.

Sanford Burnham Prebys Medical Discovery Institute, Cancer Metabolism and Signaling Networks Program, La Jolla, CA, USA.

Today, the importance of autophagy in physiological processes and pathological conditions is undeniable. Initially, autophagy merely was described as an evolutionarily conserved mechanism to maintain metabolic homeostasis in times of starvation; however, in recent years it is now apparent that autophagy is a powerful regulator of many facets of cellular metabolism, that its deregulation contributes to various human pathologies, including cancer and neurodegeneration, and that its modulation has considerable potential as a therapeutic approach. Different lipid species, including sphingolipids, sterols, and phospholipids, play important roles in the various steps of autophagy. Read More

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January 2020

Effects of Proximal Tubule Shortening on Protein Excretion in a Lowe Syndrome Model.

J Am Soc Nephrol 2020 01 1;31(1):67-83. Epub 2019 Nov 1.

Renal-Electrolyte Division, Department of Medicine,

Background: Lowe syndrome (LS) is an X-linked recessive disorder caused by mutations in , which encodes the enzyme OCRL. Symptoms of LS include proximal tubule (PT) dysfunction typically characterized by low molecular weight proteinuria, renal tubular acidosis (RTA), aminoaciduria, and hypercalciuria. How mutant causes these symptoms isn't clear. Read More

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January 2020

Lowe syndrome identified in the offspring of an oocyte donor who was an unknown carrier of a de novo mutation: a case report and review of the literature.

J Med Case Rep 2019 Nov 2;13(1):325. Epub 2019 Nov 2.

Centre of Reproduction and Genetics, Assisting Nature, Thessaloniki, Greece.

Background: Oculocerebrorenal syndrome of Lowe is an X-linked disorder with very low prevalence in the general population. The OCRL gene encodes the protein phosphatidylinositol 4,5-bisphosphate-5-phosphatase, a lipid phosphatase, located in the trans-Golgi network. Point mutations in the OCRL gene cause Lowe syndrome and Dent disease, which are characterized as a multisystemic disorder. Read More

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November 2019

Lowe syndrome with extremely short stature: growth hormone deficiency may be the pathogeny.

Growth Factors 2019 08 2;37(3-4):170-177. Epub 2019 Oct 2.

Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.

Lowe syndrome is an x-linked disorder characterized by congenital cataracts, nervous system abnormalities and renal tubular dysfunction. With the rising number of reported cases, more patients are found to suffer from endocrine abnormalities. Hereby, three Chinese patients with typical symptoms and extremely short stature were described. Read More

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Phospholipase C-related catalytically inactive protein regulates cytokinesis by protecting phosphatidylinositol 4,5-bisphosphate from metabolism in the cleavage furrow.

Sci Rep 2019 09 4;9(1):12729. Epub 2019 Sep 4.

Department of Cellular and Molecular Pharmacology, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.

Cytokinesis is initiated by the formation and ingression of the cleavage furrow. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P] accumulation followed by RhoA translocation to the cleavage furrow are prerequisites for cytokinesis progression. Here, we investigated whether phospholipase C (PLC)-related catalytically inactive protein (PRIP), a metabolic modulator of PI(4,5)P, regulates PI(4,5)P-mediated cytokinesis. Read More

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September 2019

Whole-genome sequencing revealed an interstitial deletion encompassing OCRL and SMARCA1 gene in a patient with Lowe syndrome.

Mol Genet Genomic Med 2019 09 3;7(9):e876. Epub 2019 Aug 3.

Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Background: Lowe syndrome is a rare X-linked syndrome that is characterized by involvement of the eyes, central nervous system, and kidneys. The aim of the present study was to determine the molecular basis of four patients with congenital cataract, infantile congenital hypotonia, and proximal renal tubular defect.

Methods: Four children who met the clinical manifestations of Lowe syndrome were enrolled in this study. Read More

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September 2019

Novel mutation in leading to a severe form of Lowe syndrome.

Int J Ophthalmol 2019 18;12(7):1057-1060. Epub 2019 Jul 18.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China.

Aim: To investigate the phenotype and genotype of a family with X-linked recessive Lowe syndrome.

Methods: All the members in the Chinese pedigree underwent comprehensive ophthalmologic and systemic examinations. Genomic DNA was isolated from peripheral blood of the pedigree members and 100 unrelated healthy Chinese subjects. Read More

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Lowe syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL in .

Mol Biol Cell 2019 08 19;30(17):2268-2282. Epub 2019 Jun 19.

Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.

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 reveal that, like OCRL, the OCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). Read More

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Epilepsy and cranial hemangioma in Lowe syndrome.

Acta Neurol Belg 2020 Oct 12;120(5):1199-1200. Epub 2019 Jun 12.

Neurosurgery, Sant'Anna University Hospital Ferrara, Via Aldo Moro 8, 8-44124, Cona, FE, Italy.

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October 2020

The enemy of my enemy: PTEN and PLCXD collude to fight endosomal PtdIns(4,5)P.

J Cell Biol 2019 Jul 12;218(7):2082-2083. Epub 2019 Jun 12.

Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA

Loss of the phosphoinositide 5-phosphatase OCRL causes accumulation of PtdIns(4,5)P on membranes and, ultimately, Lowe syndrome. In this issue, Mondin et al. (2019. Read More

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Cerebro- and renoprotective activities through platelet-derived biomaterials against cerebrorenal syndrome in rat model.

Biomaterials 2019 09 28;214:119227. Epub 2019 May 28.

School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address:

Though the cross-induction of either acute kidney (AKI) injury to ischemic stroke (IS) or IS to AKI might not be encountered in the early stages of cerebrorenal syndrome (CRS), both pathologies coexist in late stages. Therefore, we firstly established a late stage CRS rat model by simultaneous induction of both diseases, and further, cerebro and reno-protective activities of human platelet-rich plasma (hPRP), a blood-derived tissue engineering biomaterial, were tested in this pathology. hPRP was administrated via left common carotid artery and abdominal aorta 2 h post-sham procedure in Sprague-Dawley rats. Read More

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September 2019

Temper outbursts in Lowe syndrome: Characteristics, sequence, environmental context and comparison to Prader-Willi syndrome.

J Appl Res Intellect Disabil 2019 Sep 29;32(5):1216-1227. Epub 2019 May 29.

School of Life and Health Sciences, Aston University, Birmingham, UK.

Background: There is limited research into the nature and aetiology of temper outbursts in people with intellectual disabilities. In this study, we describe the phenomenology and environmental context of temper outbursts in Lowe syndrome, a rare genetic syndrome in which outbursts are purportedly frequent.

Method: A temper outburst interview (TOI) was conducted with caregivers of seventeen individuals with Lowe syndrome to generate an account of the behavioural sequence, common antecedents and consequences of temper outbursts, and to enable comparisons with similar work on Prader-Willi syndrome. Read More

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September 2019

PTEN reduces endosomal PtdIns(4,5)P in a phosphatase-independent manner via a PLC pathway.

J Cell Biol 2019 07 22;218(7):2198-2214. Epub 2019 May 22.

Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Canada

The tumor suppressor PTEN dephosphorylates PtdIns(3,4,5)P into PtdIns(4,5)P Here, we make the unexpected discovery that in PTEN reduces PtdIns(4,5)P levels on endosomes, independently of its phosphatase activity. This new PTEN function requires the enzymatic action of dPLCXD, an atypical phospholipase C. Importantly, we discovered that this novel PTEN/dPLCXD pathway can compensate for depletion of dOCRL, a PtdIns(4,5)P phosphatase. Read More

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[Clinical and molecular genetic analysis of a pediatric patient with Lowe syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Jun;36(6):613-615

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510623, China. Email:

Objective: To explore the genetic etiology for a child with ocular dysplasia.

Methods: Clinical examination was carried out. Medical history of the child was collected. Read More

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Guanine nucleotide exchange factors activate Rab8a for Toll-like receptor signalling.

Small GTPases 2021 Jan 7;12(1):27-43. Epub 2019 Mar 7.

Institute for Molecular Bioscience (IMB) and IMB Centre for Inflammation and Disease Research (CIDR), The University of Queensland , Brisbane, QLD, Australia.

Macrophages are important immune sentinels that detect and clear pathogens and initiate inflammatory responses through the activation of surface receptors, including Toll-like receptors (TLRs). Activated TLRs employ complex cellular trafficking and signalling pathways to initiate transcription for inflammatory cytokine programs. We have previously shown that Rab8a is activated by multiple TLRs and regulates downstream Akt/mTOR signalling by recruiting the effector PI3Kγ, but the guanine nucleotide exchange factors (GEF) canonically required for Rab8a activation in TLR pathways is not known. Read More

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January 2021

IPIP27 Coordinates PtdIns(4,5)P Homeostasis for Successful Cytokinesis.

Curr Biol 2019 03 21;29(5):775-789.e7. Epub 2019 Feb 21.

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

During cytokinesis, an actomyosin contractile ring drives the separation of the two daughter cells. A key molecule in this process is the inositol lipid PtdIns(4,5)P, which recruits numerous factors to the equatorial region for contractile ring assembly. Despite the importance of PtdIns(4,5)P in cytokinesis, the regulation of this lipid in cell division remains poorly understood. Read More

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