Bartter Syndrome Type 2 via the KCNJ1 Gene

Bartter syndrome is a group of genetically heterogeneous renal tubular disorders characterized by renal hypokalaemia, metabolic alkalosis and secondary hyperaldosteronism with normal to low blood pressure due to a renal loss of sodium (Simon et al. 1996; Scheinman et al. 1999; Brochard et al. 2009). Bartter syndrome type 2 is an antenatal condition caused by loss-of-function mutations in the potassium channel Kir 1.1 (or ROMK) encoded by the KCNJ1 gene. Common clinical features include hypercalciuria with nephrocalcinosis, maternal polyhydramnios leading to premature birth, intrauterine and postnatal polyuria, recurrent vomiting, failure to thrive and growth retardation. The presence of early transitory hyperkalaemia suggests defects in KCNJ1.

Bartter syndrome type 2 is an autosomal recessive disorder caused by defects in the KCNJ1 gene (Simon et al. 1996). KCNJ1 has two coding exons that encode the potassium channel Kir 1.1 (or ROMK), which plays an important role in potassium homeostasis. Genetic defects of KCNJ1 occur throughout the whole coding region and include missense, nonsense mutations and small deletion/insertions (Human Gene Mutation Database). Exon-level large deletions involving KCNJ1 have been also reported, but are uncommon.

This test provides full coverage of all coding exons of the KCNJ1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Detection rates of pathogenic variants in the KCNJ1 gene in a large cohort of patients with Bartter syndrome type 2 are unknown in the literature because documented KCNJ1 pathogenic variants have only been reported in limited cases.