Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/1714
Title: Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Authors: Claverie-Martín, Félix
García-Nieto, Víctor
Loris, César
Ariceta, Gema
Nadal, Inmaculada
Espinosa, Laura
Fernández-Maseda, Ángeles
Antón-Gamero, Montserrat
Ávila, África
Madrid, Álvaro
González-Acosta, Hilaria
Córdoba-Lanus, Elizabeth
Santos, Fernando
Gil-Calvo, Marta
Espino, Mar
García-Martínez, Elena
Sánchez, Ana
Muley, Rafael
metadata.dc.contributor.authoraffiliation: [Claverie-Martín,F;González-Acosta,H;Córdoba-Lanus,E]Unidad de Investigación, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.[García-Nieto,V] Nefrología Pediátrica, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.[Loris,C] Nefrología Pediátrica, Hospital Infantil Miguel Servet, Zaragoza, Spain.[Ariceta,G] Nefrología Pediátrica, Hospital de Cruces, Baracaldo, Spain. [Nadal,I] Nefrología Pediátrica, Hospital Virgen del Camino, Pamplona, Spain.[Espinosa,L] Nefrología Pediátrica, Hospital La Paz, Madrid, Spain. [Fernández-Maseda,A] Nefrología Pediátrica, Hospital Virgen de la Salud, Toledo, Spain. [Antón-Gamero,M; García-Martinez,E] Nefrología Pediátrica, Hospital Reina Sofía, Córdoba, Spain.[Avila,A] Nefrología Pediátrica, Complejo Hospitalario de Jaén, Spain. [Madrid,A] Nefrología Pediátrica, Hospital Vall d’Hebron, Barcelona, Spain.[Santos,F] Nefrología Pediátrica, Hospital Central de Asturias, Oviedo, Spain. [Gil-Calvo,M] Nefrología Pediátrica, Hospital Clínico, Santiago de Compostela, Spain.[Espino,M] Pediatría, Hospital Fundación Alcorcón, Madrid, Spain. [Sanchez,A] Nefrología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Muley,R] Nefrología Pediátrica, Hospital 12 de Octubre, Madrid, Spain.
metadata.dc.contributor.group: RenalTube Group.
Keywords: Kidneys;Magnesium;Mutation detection;Polymerase chain reaction;Renal transplantation;Substitution mutation;Riñones;Magnesio;Detección de mutaciones;Reacción en cadena de la polimerasa;Transplante renal;Mutación de sustitución
metadata.dc.subject.mesh: Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adult
Medical Subject Headings::Named Groups::Persons::Age Groups::Child::Child, Preschool
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Claudins
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::DNA Mutational Analysis
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Urological Manifestations::Hypercalciuria
Medical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Urologic Diseases::Kidney Diseases::Kidney Diseases, Cystic::Polycystic Kidney Diseases
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Malnutrition::Deficiency Diseases::Magnesium Deficiency
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, Genetic
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Calcium Metabolism Disorders::Calcinosis::Nephrocalcinosis
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Endophenotypes
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Young Adult
Medical Subject Headings::Named Groups::Persons::Age Groups::Adolescent
Issue Date: 2013
Publisher: PLOS ONE Editorial Board
Citation: Claverie-Martín F, García-Nieto V, Loris C, Ariceta G, Nadal I, Espinosa L, et al. Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. PLoS ONE. 2013;8(1):e53151
Abstract: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive tubular disorder characterized by excessive renal magnesium and calcium excretion and chronic kidney failure. This rare disease is caused by mutations in the CLDN16 and CLDN19 genes. These genes encode the tight junction proteins claudin-16 and claudin-19, respectively, which regulate the paracellular ion reabsorption in the kidney. Patients with mutations in the CLDN19 gene also present severe visual impairment. Our goals in this study were to examine the clinical characteristics of a large cohort of Spanish patients with this disorder and to identify the disease causing mutations. We included a total of 31 patients belonging to 27 unrelated families and studied renal and ocular manifestations. We then analyzed by direct DNA sequencing the coding regions of CLDN16 and CLDN19 genes in these patients. Bioinformatic tools were used to predict the consequences of mutations. Clinical evaluation showed ocular defects in 87% of patients, including mainly myopia, nystagmus and macular colobomata. Twenty two percent of patients underwent renal transplantation and impaired renal function was observed in another 61% of patients. Results of the genetic analysis revealed CLDN19 mutations in all patients confirming the clinical diagnosis. The majority of patients exhibited the previously described p.G20D mutation. Haplotype analysis using three microsatellite markers showed a founder effect for this recurrent mutation in our cohort. We also identified four new pathogenic mutations in CLDN19, p.G122R, p.I41T, p.G75C and p.G75S. A strategy based on microsequencing was designed to facilitate the genetic diagnosis of this disease. Our data indicate that patients with CLDN19 mutations have a high risk of progression to chronic renal disease.
Description: Journal Article; Research Support, Non-U.S. Gov't;
URI: http://hdl.handle.net/10668/1714
metadata.dc.relation.publisherversion: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053151
metadata.dc.identifier.doi: 10.1371/journal.pone.0053151
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Complejo Hospitalario de Jaén

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