Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 3;13(1):12587.
doi: 10.1038/s41598-023-38179-6.

Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3

Alejandro García-Castaño #  1   2 , Sara Gómez-Conde #  1   2   3 , Leire Gondra  1   2   3   4 , María Herrero  1   4 , Mireia Aguirre  1   4 , Ana-Belén de la Hoz  1   2 , Luis Castaño  1   2   3 ; Renaltube group; Leire Madariaga #  5   6   7   8
Collaborators, Affiliations

Genotypic variability in patients with clinical diagnosis of Bartter syndrome type 3

Alejandro García-Castaño et al. Sci Rep. .

Abstract

Bartter 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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Similar articles

See all similar articles

Cited by

References

    1. Konrad M, et al. Mutations in the chloride channel gene CLCNKB as a cause of classic bartter syndrome. J. Am. Soc. Nephrol. 2000;11(8):1449–1459. doi: 10.1681/ASN.V1181449. - DOI - PubMed
    1. Teulon J, et al. Exploration of the basolateral chloride channels in the renal tubule using. Nephron Physiol. 2005;99(2):p64–p68. doi: 10.1159/000082972. - DOI - PubMed
    1. Seys E, et al. Clinical and genetic spectrum of bartter syndrome type 3. J. Am. Soc. Nephrol. 2017;28(8):2540–2552. doi: 10.1681/ASN.2016101057. - DOI - PMC - PubMed
    1. Vargas-Poussou R, et al. Spectrum of mutations in gitelman syndrome. J. Am. Soc. Nephrol. 2011;22(4):693–703. doi: 10.1681/ASN.2010090907. - DOI - PMC - PubMed
    1. 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. 2014;7(3):306–310. doi: 10.1093/ckj/sfu029. - DOI - PMC - PubMed

Publication types

Substances

Supplementary concepts