[Genetic analysis of idiopathic renal hypouricemia: a case report and estimation of allelic frequency of the mutation].

Idiopathic renal hypouricemia is a hereditary disease characterized by abnormally increased renal excretion of urate. This disorder is primarily caused by a mutation of the SLC22A12 gene encoding human urate transporter 1 (URAT1). We recently encountered a case of severe hypouricemia (urate level: 0.5mg/dl in serum, 1.19g/l in urine), which was discovered when a 24-year-old male medical student was carrying out a practical examination of his own blood sample. The student was clinically healthy and showed no other abnormal laboratory findings, but his elder brother had a history of exercise-induced acute renal failure (ARF). DNA sequencing of the SLC22A12 gene demonstrated one nonsense mutation, W258X in this student. To confirm the genotype and for use in screening for W258X, we developed a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay using a mismatched primer to introduce a new HinfI restriction site into the PCR products of exon 4. The genotype of our case was then confirmed as being heterozygous, with W258X and wild-type genes. We next used this PCR-RFLP assay to examine the frequency of W258X in 64 pairs of anonymous DNA and serum samples from various Japanese patients. Three patients were found to have W258X (all heterozygous). The allelic frequency of W258X was 2.34%. Considering that hypouricemia-related ARF is frequent in children and young adults, it may be worthwhile to screen for renal hypouricemia in these age groups. Our PCR-RFLP assay may be useful for this purpose.