Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Data(s) |
12/09/2014
12/09/2014
2013
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Resumo |
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. Journal Article; Research Support, Non-U.S. Gov't; |
Identificador |
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 1932-6203 (Online) PMC3536807 http://hdl.handle.net/10668/1714 23301036 10.1371/journal.pone.0053151 |
Idioma(s) |
en |
Publicador |
PLOS ONE Editorial Board |
Relação |
PloS one http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053151 |
Direitos |
Acceso abierto |
Palavras-Chave | #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 #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 |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/published Artículo |