RT Journal Article
T1 Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
A1 Claverie-Martín, Félix
A1 García-Nieto, Víctor
A1 Loris, César
A1 Ariceta, Gema
A1 Nadal, Inmaculada
A1 Espinosa, Laura
A1 Fernández-Maseda, Ángeles
A1 Antón-Gamero, Montserrat
A1 Ávila, África
A1 Madrid, Álvaro
A1 González-Acosta, Hilaria
A1 Córdoba-Lanus, Elizabeth
A1 Santos, Fernando
A1 Gil-Calvo, Marta
A1 Espino, Mar
A1 García-Martínez, Elena
A1 Sánchez, Ana
A1 Muley, Rafael
K1 Kidneys
K1 Magnesium
K1 Mutation detection
K1 Polymerase chain reaction
K1 Renal transplantation
K1 Substitution mutation
K1 Riñones
K1 Magnesio
K1 Detección de mutaciones
K1 Reacción en cadena de la polimerasa
K1 Transplante renal
K1 Mutación de sustitución
AB 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.
PB PLOS ONE Editorial Board
YR 2013
FD 2013
LK http://hdl.handle.net/10668/1714
UL http://hdl.handle.net/10668/1714
LA en
NO 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
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 5, 2025