Late-onset Bartter syndrome type II.

Area of Science:

• Genetics
• Nephrology
• Molecular Biology

Background:

• Mutations in the KCNJ1 gene encoding the ROMK1 potassium channel cause antenatal/neonatal Bartter syndrome type II (aBS II).
• aBS II is typically a severe infantile disorder characterized by renal salt wasting, metabolic alkalosis, and nephrocalcinosis.
• This condition is generally not expected to manifest in adulthood.

Purpose of the Study:

• To report a case of late-onset Bartter syndrome type II with a mild phenotype.
• To investigate the genetic basis of this late-onset presentation using next-generation sequencing (NGS).
• To evaluate the diagnostic utility of NGS and Sanger sequencing for identifying KCNJ1 mutations.

Main Methods:

• Targeted massively parallel sequencing (NGS) and Sanger sequencing were employed for mutation analysis.
• Bioinformatics approaches were used to analyze sequencing data.
• Clinical and molecular data from a patient with late-onset Bartter syndrome were analyzed.

Main Results:

• A female patient presented with a mild, late-onset form of Bartter syndrome type II.
• Compound heterozygous KCNJ1 mutations, including a novel c.197T > A (p.I66N) and a known c.875G > A (p.R292Q), were identified.
• NGS combined with Sanger sequencing proved effective for molecular diagnosis.

Conclusions:

• Antenatal/neonatal Bartter syndrome type II should be considered in patients with late-onset phenotypes.
• NGS is a reliable method for molecular diagnosis of aBS II, even in atypical presentations.
• Accurate genetic diagnosis has significant implications for differential diagnosis and patient management, particularly for nephrocalcinosis and congenital renal electrolyte abnormalities.