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Description of the novel variant c.784delG;p. (Ala262Profs*68) at BSND gene and its association with Bartter Syndrome Type Iva

  • Authors:
    • Jéssica Hilário Bonomo
    • Lívia Cláudio De Oliveira
    • Maria Do Carmo Sorci Dias Scher
    • Anderson Ferreira Da Cunha
    • Amélia Trindade
  • View Affiliations / Copyright

    Affiliations: Laboratory of Biochemistry and Applied Genetics, Department of Genetics and Evolution, Center for Biological and Health Sciences, Federal University of São Carlos, São Carlos, São Paulo 13565‑905, Brazil, Unit of Ambulatory Pediatrics, University Hospital of Brasilia, University of Brasilia, Brasilia 70840‑901, Brazil, Medicine course, University Center of Brasilia (UniCEUB), Brasilia 70790‑075, Brazil, Department of Medicine, Center for Biological and Health Sciences, Federal University of São Carlos, São Carlos, São Paulo, 13565‑905, Brazil
    Copyright: © Bonomo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 49
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    Published online on: February 19, 2026
       https://doi.org/10.3892/br.2026.2122
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Abstract

Bartter syndrome (BS) is a group of diseases caused by variants in genes related to salt reabsorption in the thick ascending limb of the loop of Henle. It causes dysregulation in salt homeostasis and is characterized by hyperplasia and hypertrophy of the juxtaglomerular apparatus, hyperaldosteronism, hypokalemic alkalosis and impaired growth and development. BS type IVa is caused by variants in BSND, which encodes Barttin, a subunit for chloride channels (CLC). This specific subtype also causes sensorineural deafness due to its impact on CLC‑kidney a (Ka), a channel important for the production of endolymph in the inner ear. In the present study, the case of a Brazilian girl diagnosed with BS Iva was presented, whose molecular diagnosis revealed a novel variant, c.784delG;p.(Ala262Profs*68), compound heterozygous with c.139G>A;p.Gly47Arg. This novel variant appears to be the first BS IVa causing variant described in exon 4, which encodes for the later part of the cytoplasmatic C‑terminal unstructured tail. In silico analysis of this variant predicted the resulting frameshift as disease causing, due to alteration in significant portion of the protein. While the authors suggest this variant may cause erroneous membrane sorting of the CLC type channels, further studies are necessary to elucidate the mechanism.
View Figures

Figure 1

BSND variants found in patient
using Sanger sequencing. The variant (A) c.139G>A;p.Gly47Arg
(rs74315289) in exon 1 and (B) c.784delG;p.(Ala262Profs*68) at exon
4 of the BSND gene from an affected female individual.
Arrows indicate the nucleotide change in exon 1 or the location of
the deletion in the sequence of exon 4.

Figure 2

Bartter type IVa causing variants in
the BSND gene and Barttin protein. Schematic of the position
of the known variants and their position in the protein (missense
and nonsense SNPs, and frameshifts) and coding sequence (loss of
exons and splicing variants).

Figure 3

Sequence homology analysis of (A)
BSND coding sequence and (B) Barttin amino acid sequence.
Analysis was performed with c.139G>A;p.Gly47Arg,
c.784delG;p.(Ala262Profs*68), wild type and primates with >90%
protein identity with wild-type human Barttin obtained from
BLAST.
View References

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Bonomo JH, De Oliveira LC, Scher MD, Da Cunha AF and Trindade A: Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva. Biomed Rep 24: 49, 2026.
APA
Bonomo, J.H., De Oliveira, L.C., Scher, M.D., Da Cunha, A.F., & Trindade, A. (2026). Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva. Biomedical Reports, 24, 49. https://doi.org/10.3892/br.2026.2122
MLA
Bonomo, J. H., De Oliveira, L. C., Scher, M. D., Da Cunha, A. F., Trindade, A."Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva". Biomedical Reports 24.4 (2026): 49.
Chicago
Bonomo, J. H., De Oliveira, L. C., Scher, M. D., Da Cunha, A. F., Trindade, A."Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva". Biomedical Reports 24, no. 4 (2026): 49. https://doi.org/10.3892/br.2026.2122
Copy and paste a formatted citation
x
Spandidos Publications style
Bonomo JH, De Oliveira LC, Scher MD, Da Cunha AF and Trindade A: Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva. Biomed Rep 24: 49, 2026.
APA
Bonomo, J.H., De Oliveira, L.C., Scher, M.D., Da Cunha, A.F., & Trindade, A. (2026). Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva. Biomedical Reports, 24, 49. https://doi.org/10.3892/br.2026.2122
MLA
Bonomo, J. H., De Oliveira, L. C., Scher, M. D., Da Cunha, A. F., Trindade, A."Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva". Biomedical Reports 24.4 (2026): 49.
Chicago
Bonomo, J. H., De Oliveira, L. C., Scher, M. D., Da Cunha, A. F., Trindade, A."Description of the novel variant c.784delG;p. (Ala262Profs*68) at <em>BSND</em> gene and its association with Bartter Syndrome Type Iva". Biomedical Reports 24, no. 4 (2026): 49. https://doi.org/10.3892/br.2026.2122
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