Prenatal diagnosis of HPRT mutant genes in Lesch-Nyhan syndrome

Lesch-Nyhan syndrome is an X-linked recessive disorder characterized by hyperuricemia, physical and mental retardation, choreoathetosis, and compulsive self-mutilation.1 This disease is associated with the complete absence of activity of an enzyme involved in purine metabolism, hypoxanthine guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8).2 Partial HPRT deficiency generally presents as gout and uric acid overproduction in early adulthood.3 The marked genetic heterogeneity of HPRT deficiency is well known. As reviewed previously by Sculley et al.,4 many different mutations at the HPRT gene locus (deletions, insertions, duplications, abnormal splicing, and point mutations at different sites of the coding region from exon 1 to 9) have been reported. We have identified Japanese and Korean HPRT mutants,5–12 including two rare cases in female subjects,5,9 by polymerase chain reaction of reverse-transcribed mRNA (RT-PCR) and the multiplex amplification technique of all nine HPRT exons from the genomic DNA coupled with direct sequencing. In this study, we report prenatal diagnoses of HPRT mutant genes which have been carried out in five Lesch-Nyhan families.