Carrier detection of partial hypoxanthine-guanine phosphoribosyltransferase deficiency by analysis with BamHI restriction fragment length polymorphisms and oligonucleotide probes.

Hyperuricemic nephropathy can progress to the permanent renal damage even in infancy in partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. We have encountered two unrelated patients with partial HPRT deficiency, and found that early detection of the disease and long-term management for hyperuricemia were necessary to prevent renal impairment. The HPRT gene is situated in the q26-27 region of the long arm of the X-chromosome, and females with mutant HPRT alleles are heterozygous for the disease, and they develop gout after menopause. We undertook the investigation of carriers in the two patients' families, using BamHI restriction fragment length polymorphisms and oligonucleotide probes that recognized the specific mutations within the HPRT gene. We also demonstrated that the allele frequencies of BamHI restriction fragment length polymorphisms in 62 Japanese females were 0.36 for the 22-kb/25-kb allele, 0.41 for the 12-kb/25-kb allele, and 0.23 for the 22-kb/18-kb allele, resulting in a heterozygous state in 66% of females.