The first case of familial Lesch-Nyhan variant in Japan revealed by molecular genetic examination

Abstract

Lesch-Nyhan disease is sex-linked recessive disorder of children occurring at a very young age and a rare condition that results in severe hyperuricemia, motor disability, developmental delay, and self-injurious behavior. These conditions are attributed to congenital deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), and individuals with less severe problems are called Lesch-Nyhan variants (LNV). We diagnosed a young man who had hyperuricemia and gout, and his two brothers who also had hyperuricemia as LNV. Molecular analysis of the three brothers clarified a point mutation of c.59A>T (p.D20V) in their HPRT gene (HPRT1) and their enzymatic activities were under the detection limits. Their mother was heterozygous for the mutant HPRT1. Regarding point mutations of HPRT1 in LNV, 120 cases have been reported. The point mutation of c.59A>T had already been reported in 1991 in The United States, but it was only a single case. We have detected the mutation in one family, and this is the first report from Japan.