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5 results on '"MESH: Oculocerebrorenal Syndrome"'

1. From lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes

Author

Anne Blanchard, Joël Lunardi, Haifa Hichri, Rémi Salomon, Michel Remesy, Rosa Vargas Poussou, Geneviève Baujat, Nicole Monnier, Charles Coutton, Bruno Ranchin, Véronique Satre, Olivier Dorseuil, John Rendu, François Nobili, Biochimie et Genetique Moleculaire, CHU Grenoble, Laboratoire de Genetique Chromosomique, [Institut Cochin] Département Développement, Reproduction et Cancer (DRC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dpt de Genetique, Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Investigation Clinique, Service de nephrologie pédiatrique, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre de Référence des Maladies Rénales Rares, Hospices Civil de Lyon, Service de Nephrologie, CHU Toulouse [Toulouse], Service de néphrologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, [Institut Cochin] Département Développement, Reproduction et Cancer ( DRC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Laboratoire de Génétique Chromosomique [CHU de Grenoble], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de biochimie et génétique moléculaire, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de biochimie et génétique moléculaire, CHU Grenoble-CHU Grenoble, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence des Maladies Rénales Héréditaires de l'enfant et de l'adulte, Agence National de la Recherche, GIS-Maladies Rares, Association du Syndrome de Lowe and Fondation Daniel Ducoin, R.V.-P. and A.B. are supported by EUNEFRON (FP7, GA]201590) programs of the R.V.-P. and A.B. are supported by EUNEFRON (FP7, GA#201590) programs of the European Community., European Project: 201590,EC:FP7:HEALTH,FP7-HEALTH-2007-A,EUNEFRON(2008), Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Roux-Buisson, Nathalie, and European Network for the Study of Orphan Nephropathies - EUNEFRON - - EC:FP7:HEALTH2008-05-01 - 2012-04-30 - 201590 - VALID

Subjects
Male, MESH: Dent Disease, MESH: Mutation, Oculocerebrorenal syndrome, DNA Mutational Analysis, Nonsense mutation, 030232 urology & nephrology, Dent Disease, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Protein degradation, Biology, MESH: Phenotype, medicine.disease_cause, Frameshift mutation, 03 medical and health sciences, 0302 clinical medicine, Chloride Channels, Genetics, medicine, Humans, Missense mutation, RNA, Messenger, MESH: DNA Mutational Analysis, Genetics (clinical), MESH: RNA, Messenger, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, Mutation, MESH: Humans, MESH: Chloride Channels, Life Sciences, medicine.disease, Phosphoric Monoester Hydrolases, MESH: Male, 3. Good health, Oculocerebrorenal Syndrome, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Phosphoric Monoester Hydrolases, OCRL, MESH: Oculocerebrorenal Syndrome
Abstract

International audience; Mutations of OCRL1 are associated with both the oculocerebrorenal syndrome Lowe, a multi-systemic and Dent-2 disease, a renal tubulopathy. We have identified a mutation in 130 Lowe syndrome families and 6 affected by Dent-2 disease with 51 of these mutations being novel. No founding effect was evidenced for recurrent mutations. Two mutations initially reported as causing Dent-2 disease were identified in patients, including two brothers, presenting with Lowe syndrome thus extending the clinical variability of OCRL1 mutations. mRNA levels, protein content and PiP2-ase activities were analyzed in patient's fibroblasts. Although mRNA levels were normal in cells harbouring a missense mutation, the OCRL1 content was markedly lowered suggesting that enzymatic deficiency resulted mainly from protein degradation rather than a catalytic inactivation as usually reported. Analysis of a splicing mutation that led to the elimination of the initiation codon evidenced the presence of shortened forms of OCRL1 that might result from the use of alternative initiation codons. The specific mapping of the frameshift and nonsense mutations, exclusively identified in exons 1-7 and exons 8-23 respectively for Dent disease and Lowe syndrome together with the possible use of alternative initiation codons might be related to their clinical expression i.e. Lowe syndrome or Dent-2 disease.

Published
2011
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2. Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders

Author

Lasne, Dominique, Baujat, Geneviève, Mirault, Tristan, Lunardi, Joël, Grelac, Françoise, Egot, Marion, Salomon, Rémi, Bachelot-Loza, Christilla, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Risque Thrombotique et Mecanismes de l'Hemostase (U765), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de néphrologie pédiatrique [CHU Necker], Association du Syndrome de Lowe GIS-Maladies Rares INSERM, Roux-Buisson, Nathalie, Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Risque Thrombotique et Mecanismes de l'Hemostase ( U765 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Risque Thrombotique et Mécanismes de l'Hémostase (U765)

Subjects
Male, MESH : Retrospective Studies, MESH : Phosphoric Monoester Hydrolases, MESH : Hemostatic Disorders, MESH: GTPase-Activating Proteins, MESH : Child, Preschool, MESH : Child, MESH: Child, Child, Hemostatic Disorders, GTPase-Activating Proteins, MESH: Genetic Predisposition to Disease, MESH : Infant, MESH: Infant, Child, Preschool, platelets, RhoGAP, MESH: Phosphoric Monoester Hydrolases, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Blood Coagulation Tests, MESH : Mutation, MESH: Oculocerebrorenal Syndrome, MESH: Mutation, Adolescent, MESH : Male, MESH : Blood Coagulation Tests, haemostasis disorders, MESH: Hemostatic Disorders, MESH : Adolescent, Humans, MESH : Oculocerebrorenal Syndrome, Genetic Predisposition to Disease, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Retrospective Studies, MESH: Adolescent, OCRL, MESH: Humans, MESH : Humans, MESH: Blood Coagulation Tests, MESH: Child, Preschool, Infant, MESH : GTPase-Activating Proteins, MESH: Retrospective Studies, Phosphoric Monoester Hydrolases, MESH: Male, Lowe syndrome, Oculocerebrorenal Syndrome, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mutation, MESH : Genetic Predisposition to Disease
Abstract

International audience; Lowe syndrome (LS) is a rare X-linked disorder caused by mutations in the oculocerebrorenal gene (OCRL), encoding OCRL, a phosphatidylinositol 5-phosphatase with a RhoGAP domain. An abnormal rate of haemorrhagic events was found in a retrospective clinical survey. Herein, we report the results of exploration of haemostasis in six LS patients. All patients had normal coagulation tests but prolonged closure times (CTs) in the PFA-100 system. Healthy donors' blood samples incubated with a RhoA kinase inhibitor had prolonged CTs. This suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in LS.

Published
2010
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3. Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1

Author

Laura E. Swan, Livia Tomasini, Joël Lunardi, Pietro De Camilli, Michelle Pirruccello, Department of Cell Biology [New Haven], Yale University School of Medicine-Howard Hughes Medical Institute (HHMI), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), DA018343/DA/NIDA NIH HHS/United States DK082700/DK/NIDDK NIH HHS/United States DK45735/DK/NIDDK NIH HHS/United States NS36251/NS/NINDS NIH HHS/United States Howard Hughes Medical Institute/United States, Yale School of Medicine [New Haven, Connecticut] (YSM)-Howard Hughes Medical Institute (HHMI), and Roux-Buisson, Nathalie

Subjects
Leucine zipper, MESH: Vesicular Transport Proteins, Endosome, Oculocerebrorenal syndrome, Amino Acid Motifs, Molecular Sequence Data, Endocytic cycle, Mutation, Missense, Vesicular Transport Proteins, Dent Disease, MESH: Carrier Proteins, Endosomes, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Amino Acid Sequence, Biology, 03 medical and health sciences, MESH: Amino Acid Motifs, MESH: Protein Structure, Tertiary, 0302 clinical medicine, medicine, Humans, Amino Acid Sequence, Conserved Sequence, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Genetics, 0303 health sciences, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, MESH: Conserved Sequence, MESH: Humans, MESH: Molecular Sequence Data, Biological Sciences, medicine.disease, Endocytosis, Phosphoric Monoester Hydrolases, Protein Structure, Tertiary, Pleckstrin homology domain, Oculocerebrorenal Syndrome, MESH: Endosomes, MESH: Endocytosis, MESH: Phosphoric Monoester Hydrolases, OCRL, Carrier Proteins, Phosphotyrosine-binding domain, 030217 neurology & neurosurgery, MESH: Oculocerebrorenal Syndrome
Abstract

International audience; Mutations of the inositol 5' phosphatase oculocerebrorenal syndrome of Lowe (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal tubule reabsorption, and additional nervous system and ocular defects in the case of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Activating Domain-like) domain of OCRL. The interaction is mediated by a short amino acid motif similar to that used by the rab-5 effector APPL1 (Adaptor Protein containing pleckstrin homology [PH] domain, PTB domain and Leucine zipper motif 1) APPL1 for OCRL binding. Ses binding is mutually exclusive with APPL1 binding, and is disrupted by the same missense mutations in the ASH-RhoGAP-like domain that also disrupt APPL1 binding. Like APPL1, Ses1 and -2 are localized on endosomes but reside on different endosomal subpopulations. These findings define a consensus motif (which we have called a phenylalanine and histidine [F&H] motif) for OCRL binding and are consistent with a scenario in which Lowe syndrome and Dent disease result from perturbations at multiple sites within the endocytic pathway.

Published
2010
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4. Mutations in OCRL1 gene in Indian children with Lowe syndrome

Author

Sidharth Kumar Sethi, Pankaj Hari, Ashima Gulati, Neerja Gupta, Joël Lunardi, Arvind Bagga, Department of Pediatrics, Division of Pediatric Nephrology and Genetics, All India Institute of Medical Sciences, Department of Pediatrics, Genetics Unit, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Roux-Buisson, Nathalie

Subjects
Male, Physiology, DNA Mutational Analysis, 030232 urology & nephrology, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Exon, 0302 clinical medicine, Prenatal Diagnosis, MESH: Child, Missense mutation, MESH: Codon, Nonsense, MESH: DNA Mutational Analysis, Child, Frameshift Mutation, Genetics, 0303 health sciences, Mutation, Renal tubular acidosis, MESH: Frameshift Mutation, Exons, 3. Good health, Codon, Nonsense, Nephrology, Child, Preschool, MESH: Phosphoric Monoester Hydrolases, MESH: Genetic Counseling, MESH: Oculocerebrorenal Syndrome, Oculocerebrorenal syndrome, Genetic counseling, Nonsense mutation, Mutation, Missense, India, Genetic Counseling, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Frameshift mutation, 03 medical and health sciences, Physiology (medical), medicine, Humans, MESH: Prenatal Diagnosis, Gene, 030304 developmental biology, MESH: Mutation, Missense, [SDV.GEN]Life Sciences [q-bio]/Genetics, OCRL1 gene, MESH: Humans, MESH: Child, Preschool, medicine.disease, Phosphoric Monoester Hydrolases, MESH: Male, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: India, MESH: Exons
Abstract

International audience; BACKGROUND: Lowe syndrome is an X-linked disorder secondary to mutations involving the OCRL1 gene. There are no data on the spectrum of the disease in the Asian population. METHODS: Detailed clinical assessment, a laboratory assessment which included both glomerular and tubular function tests and genomic DNA analysis, was carried out in six unrelated patients with Lowe syndrome. RESULTS: Analysis of this gene in six unrelated patients with Lowe syndrome showed novel mutations in four and previously described mutations in two. These included a missense mutation (exon 10), two nonsense mutations (exons 10 and 21), two frameshift mutations (exons 12 and 21) and a mutation at the acceptor site of intron 22. The mothers were found to be heterozygote carriers in four cases. CONCLUSIONS: This is the first report of mutations involving the OCRL1 gene in patients with Lowe syndrome of Indian origin. These observations have implications for genetic counseling and prenatal diagnosis for families with Lowe syndrome.

Published
2008
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5. [Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]

Author

Chabaâ, Laïla, Monnier, Nicole, Dahri, Saloua, Jorio, M., Lunardi, Joël, Chabraoui, Layachi, Roux-Buisson, Nathalie, Laboratoire de biochimie, Hôpital d'enfants de Rabat, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de pédiatrie, Ce travail a été réalisé en partie grâce au financement (NM) par le GIS-Maladies Rares et l'Association du Syndrome de Lowe., and Collaboration

Subjects
Male, MESH: Sequence Homology, Amino Acid, Molecular Sequence Data, MESH: Sequence Alignment, Mutation, Missense, MESH: Amino Acid Sequence, MESH: Base Sequence, Animals, Humans, MESH: Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amino Acid Sequence, OCRL1, Sequence Deletion, MESH: Mutation, Missense, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Sequence Homology, Amino Acid, syndrome de Lowe, Infant, MESH: Sequence Deletion, MESH: Amino Acid Substitution, MESH: Infant, MESH: Male, Phosphoric Monoester Hydrolases, Morocco, Oculocerebrorenal Syndrome, Amino Acid Substitution, MESH: Morocco, 5 biphosphate 5-phosphatase, MESH: Phosphoric Monoester Hydrolases, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], inositol 4, mutation, Sequence Alignment, MESH: Oculocerebrorenal Syndrome
Abstract

International audience; 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.

Published
2005

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