Clinical and genetic characteristics of the patients with hypertension and hypokalemia carrying a novel SCNN1A mutation

Abstract

The objective of this study was to clinically and genetically characterize a pedigree with Liddle syndrome (LS). A LS pedigree comprising with one proband and seven family members was enrolled. The subjects’ symptoms, laboratory results and genotypes were analyzed. Peripheral venous samples were collected from the subjects, and genomic DNA was extracted. DNA library construction and exome capture were performed on an Illumina HiSeq 4000 platform. The selected variant sites were validated using Sanger sequencing. The mutation effects were investigated using prediction tools. The proband and her paternal male family members had mild hypertension, hypokalemia and muscle weakness, including the absence of low renin and low aldosterone. Genetic analysis revealed that the proband carried a compound heterozygous mutation in SCNN1A, a novel heterozygous mutation, c.1130T > G (p.Ile377Ser) and a previously characterized polymorphism, c.1987A > G (p.Thr633Ala). The novel mutation site was inherited in an autosomal dominant manner and was predicted by in silico tools to exert a damaging effect. Alterations in the SCNN1A domain were also predicted by protein structure modeling. After six months of follow-up, treatment had significantly improved the patient’s limb weakness and electrolyte levels. The novel mutation c.1130T > G of the SCNN1A gene was detected in the pedigree with LS. The clinical manifestations of the pedigree were described, which expand the phenotypic spectrum of LS. This result of this study also emphasizes the value of genetic testing for diagnosing LS.

Keywords:

• Hypertension
• hypokalemia
• Liddle syndrome
• gene
• mutation

Acknowledgments

We thank the patients and their family members for agreeing to participate in this study.

Author contributions

Shaogang Ma conceived the project. Mengzi Chen and Xi Lv wrote the manuscript. Mengzi Chen and Xi Lv performed the data collection and analysis. Jiwu Li and Manli Guo contributed to the development of the paper and provided detailed input on drafts. All authors contributed to the paper as it evolved and approved the final version.

Disclosure statement

No potential conflict of interest was reported by the author(s).