Key result
SCNN1B frameshift mutation linked to Liddle syndrome with varied phenotypes in an extended Chinese family.
Why the study?
Liddle syndrome is a rare autosomal dominant disease caused by ENaC subunit mutations, and this study aimed to identify the mutation responsible for the disease in an extended Chinese family.
Observational (n=20)
Identification of a frameshift mutation (c.1806dupG) in the SCNN1B gene causing Liddle syndrome highlights the importance of early genetic diagnosis to enable tailored therapy with amiloride.
Supports targeted genetic testing in suspected Liddle families; extends known SCNN1B variants but remains hypothesis-generating pending larger studies.
BACKGROUND/AIMS: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. METHODS: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the β-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. RESULTS: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated β-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. CONCLUSIONS: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of β-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.
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Fan et al. (2019) conducted an observational in Liddle syndrome (n=20). SCNN1B exon 13 mutation (c.1806dupG) was evaluated on Identification of the mutation responsible for Liddle syndrome. A frameshift mutation (c.1806dupG) in the SCNN1B gene was identified as the cause of Liddle syndrome in 9 members of an extended Chinese family, presenting with varied phenotypes.