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