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Case Reports
. 2022 Oct;10(10):e2027.
doi: 10.1002/mgg3.2027. Epub 2022 Aug 1.

A novel CLCNKB variant in a Chinese family with classic Bartter syndrome and prenatal genetic diagnosis

Qianying Zhao  1   2 , Qinqin Xiang  1   2 , Yu Tan  1   2 , Xiao Xiao  1   2 , Hanbing Xie  1   2 , He Wang  1   2 , Mei Yang  1   2 , Shanling Liu  1   2
Affiliations
Case Reports

A novel CLCNKB variant in a Chinese family with classic Bartter syndrome and prenatal genetic diagnosis

Qianying Zhao et al. Mol Genet Genomic Med. 2022 Oct.

Abstract

Background: Type III Bartter syndrome (BS), often known as classic Bartter syndrome is caused by variants in CLCNKB gene, which encoding the basolateral chloride channel protein ClC-Kb, and is characterized by renal salt wasting, hypokalemia, metabolic alkalosis, increased renin, and aldosterone levels.

Methods: A 2-year-old boy presented severe malnutrition, severe metabolic alkalosis and severe hypokalemia and was clinically diagnosed with BS. The trio exome sequencing (ES) was performed to discover the genetic cause of this patient, followed by validation using Sanger sequencing and quantitative polymerase chain reaction subsequently.

Results: The genetic analysis indicated that this patient with a compound heterozygous variants of CLCNKB gene including a novel nonsense variant c.876 T > A and a whole-gene deletion. The two variants were inherited from his parents, respectively. Subsequently, target sequencing of CLCNKB gene was performed for next pregnancy, and prenatal genetic diagnosis was provided for the family.

Conclusions: The results of current study identified the compound heterozygous variants in a patient with classic BS. The novel variant expands the spectrum of CLCNKB variants in BS. Our study also indicates that ES is an alternative tool to simultaneously detect single-nucleotide variants and copy-number variants.

Keywords: CLCNKB; classic Bartter syndrome; exome sequencing; prenatal genetic diagnosis.

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Conflict of interest statement

The authors declare no conflict of interests.

Figures

FIGURE 1
FIGURE 1
The pedigree of the present family. The proband is indicated by an arrow.
FIGURE 2
FIGURE 2
Validation and gene dosage effect of variants in CLCNKB. (a) Sanger sequencing confirmed variant (c.876 T > A) in this family. (b) qPCR showed significant decrease of CLCNKB expression (exon 10 and exon 18) in the proband, the fetus and their mother. All the values are means ± SEM from three independent experiments, and statistical analysis was performed by one‐way ANOVA.
See this image and copyright information in PMC

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