Identification of a Novel CLCNKB Mutation in an Iranian Family with Bartter Syndrome Type ۳.

Bartter syndrome (BS) is a group of uncommon genetic disorders of reabsorption of salt in the cortical thick ascending limb (TAL) of the Henle's loop, typically distinguished by metabolic alkalosis, salt loss, hypokalemia, hyperreninemic hyperaldosteronism and normal blood pressure. Bartter syndrome type ۳, recognized as a classic BS (CBS), occurs because of mutations in CLCNKB gene. We enrolled one consanguineous Iranian family with one patient in our study. Targeted genomic capture and massively parallel sequencing (MPS) of all recognized genes responsible for BS subtypes ۱–۵ were carried out to recognize the genetic reasons of BS. Here, we report the recognition of a novel homozygous frameshift mutation in the CLCNKB gene in an Iranian pedigree. The subjects were homozygous for a frameshift mutation (p.Gly۶۶۲GlyfsX۱۲) within CLCNKB gene that encodes the basolateral chloride voltage-gated channel Kb. The identification of other causative mutations in CLCNKB gene additionally supports the important function of this gene in causing BS. To the best of our knowledge, this is a novel CLCNKB gene mutation in BS children.The accurate function of the CLCNKB Gly۶۶۲GlyfsX۱۲ mutation in the CBS pathogenesis  is still unknown.

Keywords:

Bartter syndrome , mutation , CLCNKB , Whole exome sequencing