Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3
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Published:2023-08-03
Issue:1
Volume:13
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
García-Castaño Alejandro, Gómez-Conde Sara, Gondra Leire, Herrero María, Aguirre Mireia, de la Hoz Ana-Belén, Castaño Luis, Santos Fernando, Gil-Peña Helena, Coto Eliecer, Loredo Vanessa, Ordóñez Flor Ángel, Rodríguez Julián, Braga Eva, Hernández Olaya, Fuente Rocío, Claramunt Débora, García-Nieto Víctor Manuel, Claverie-Martín Félix, Ramos-Trujillo Elena, Luis-Yanes Maria Isabel, Córdoba-Lanús Elizabeth, Perdomo-Ramirez Ana, Mura-Escorche Gloria, Castaño Luis, Madariaga Leire, Pérez de Nanclares Gustavo, García-Castaño Alejandro, Aguirre Mireia, Gondra Leire, Herrero María, Aguayo Aníbal, García-Pérez Nélida, Ariceta Gema, Meseguer Anna, Cantero Gerard, Cantos-Pastor Virginia, Pérez-González Elena, Bello-Gutiérrez Pablo, Madariaga LeireORCID,
Abstract
AbstractBartter syndrome (BS) is a salt-losing hereditary tubulopathy characterized by hypokalemic metabolic alkalosis with secondary hyperaldosteronism. Confirmatory molecular diagnosis may be difficult due to genetic heterogeneity and overlapping of clinical symptoms. The aim of our study was to describe the different molecular findings in patients with a clinical diagnosis of classic BS. We included 27 patients (26 families) with no identified pathogenic variants in CLCNKB. We used a customized Ion AmpliSeq Next-Generation Sequencing panel including 44 genes related to renal tubulopathies. We detected pathogenic or likely pathogenic variants in 12 patients (44%), reaching a conclusive genetic diagnosis. Variants in SLC12A3 were found in 6 (Gitelman syndrome). Median age at diagnosis was 14.6 years (range 0.1–31), with no history of prematurity or polyhydramnios. Serum magnesium level was low in 2 patients (33%) but urinary calcium excretion was normal or low in all, with no nephrocalcinosis. Variants in SLC12A1 were found in 3 (BS type 1); and in KCNJ1 in 1 (BS type 2). These patients had a history of polyhydramnios in 3 (75%), and the mean gestational age was 34.2 weeks (SD 1.7). The median age at diagnosis was 1.8 years (range 0.1–6). Chronic kidney disease and nephrocalcinosis were present in 1 (25%) and 3 (75%) patients, respectively. A variant in CLCN5 was found in one patient (Dent disease), and in NR3C2 in another patient (Geller syndrome). Genetic diagnosis of BS is heterogeneous as different tubulopathies can present with a similar clinical picture. The use of gene panels in these diseases becomes more efficient than the study gene by gene with Sanger sequencing.
Funder
Instituto de Salud Carlos III Osasun Saila, Eusko Jaurlaritzako Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference35 articles.
1. Konrad, M. et al. Mutations in the chloride channel gene CLCNKB as a cause of classic bartter syndrome. J. Am. Soc. Nephrol. 11(8), 1449–1459 (2000). 2. Teulon, J. et al. Exploration of the basolateral chloride channels in the renal tubule using. Nephron Physiol. 99(2), p64–p68 (2005). 3. Seys, E. et al. Clinical and genetic spectrum of bartter syndrome type 3. J. Am. Soc. Nephrol. 28(8), 2540–2552 (2017). 4. Vargas-Poussou, R. et al. Spectrum of mutations in gitelman syndrome. J. Am. Soc. Nephrol. 22(4), 693–703 (2011). 5. Larkins, N., Wallis, M., McGillivray, B. & Mammen, C. A severe phenotype of Gitelman syndrome with increased prostaglandin excretion and favorable response to indomethacin. Clin. Kidney J. 7(3), 306–310 (2014).
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