Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) Deficiencies: HPRT1 Mutations in New Japanese Families and PRPP Concentration

Abstract

Mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch–Nyhan syndrome, which is characterized by hyperuricemia, severe motor disability, and self-injurious behavior, or HPRT-related gout with hyperuricemia. Four mutations were detected in two Lesch–Nyhan families and two families with partial deficiency since our last report. A new mutation of G to TT (c.456delGinsTT) resulting in a frameshift (p.Q152Hfs*3) in exon 3 has been identified in one Lesch–Nyhan family. In the other Lesch–Nyhan family, a new point mutation in intron 7 (c.532 + 5G > T) causing splicing error (exon 7 excluded, p.L163Cfs*4) was detected. In the two partial deficiency cases with hyperuricemia, two missense mutations of p.D20V (c.59A > T) and p.H60R (c.179A >G) were found. An increase of erythrocyte PRPP concentration was observed in the respective phenotypes and seems to be correlated with disease severity.

Keywords:

• HPRT
• mutations
• Lesch–Nyhan syndrome
• PRPP concentration