Pathogenic Variants of (URAT1) and (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of Variant c.374C>T; p.(T125M).

Renal hypouricemia (RHUC) is a rare inherited disorder characterized by impaired urate reabsorption in the proximal tubule resulting in low urate serum levels and increased urate excretion. Some patients may present severe complications such as exercise-induced acute renal failure and nephrolithiasis. RHUC is caused by inactivating mutations in the (RHUC type 1) or (RHUC type 2) genes, which encode urate transporters URAT1 and GLUT9, respectively. In this study, our goal was to identify mutations associated with twenty-one new cases with RHUC through direct sequencing of and coding exons. Additionally, we carried out an SNPs-haplotype analysis to determine whether the rare variant c.374C>T; p.(T125M), which is recurrent in Spanish families with RHUC type 2, had a common-linked haplotype. Six intragenic informative SNPs were analyzed using PCR amplification from genomic DNA and direct sequencing. Our results showed that ten patients carried the mutation c.1400C>T; p.(T467M), ten presented the mutation c.374C>T, and one carried a new heterozygous mutation, c.593G>A; p.(R198H). Patients carrying the mutation c.374C>T share a common-linked haplotype, confirming that it emerged due to a founder effect.