Nephrolithiasis via the SLC26A1 Gene

Nephrolithiasis is a clinical condition in which urinary supersaturation leads to stone formation in the urinary system (the lumen of the collecting system, ureter, and bladder) (Braun et al. 2016; Halbritter et al. 2015; Gee et al. 2016). Patients with kidney stones may have no symptoms or may present with flank pain, gross or microscopic hematuria, obstruction of one or both kidneys, and urinary infections. It affects 10%-15% of adults in their lifetime. Defects in the SLC26A1 gene cause calcium oxalate nephrolithiasis (Gee et al. 2016). The index patient reported by Gee et al. presented with acute renal failure due to ureteral obstruction with calculi at the age of five.

SLC26A1-associated nephrolithiasis is an autosomal recessive disorder (Gee et al. 2016). The SLC26A1 gene (two coding exons) encodes solute carrier family 26 member 1, which plays a critical role in oxalate and sulfate homeostasis. To date, documented genetic defects of SLC26A1 for nephrolithiasis are only missense variants that result in decreased transporter activity (Human Gene Mutation Database). A large deletion encompassing SLC26A1 has been reported in a study of epileptic encephalopathies, but the contribution of SLC26A1 to disease is uncertain (Mefford et al. 2011).

In the original report of SLC26A1-associated nephrolithiasis, 2 out of 348 (~0.6%) unrelated patients with kidney stones were found to have biallelic pathogenic SLC26A1 variants (Gee et al. 2016).

This test provides full coverage of all coding exons of the SLC26A1 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).