Identification of a new single nucleotide substitution on the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTTsou)from a Taiwanese aboriginal family with severe gout

Objective. A new single nucleotide change of the hypoxanthine-guanine phosp horibosyltransferase (HPRT) gene on coding region has been identified from a Taiwanese aboriginal family with gout, The mutation was used to screen 27 members of the family, 22 Tsou, 70 Atayal, and 76 Bunun children, the elde rs for whom had been found to have a high prevalence of gout. Methods. An entire peptide of HPRT coding region was directly sequenced fro m the cDNA of a patient with severe gout, and by using polymerase chain rea ction and restriction fragment length polymorphism to screen the other part icipants. Results, A new nucleotide change located at nucleotide 152 (G to A transiti on) was found that predicted an arginine to glutamine substitution at amino acid 51. This variant was named HPRTTsou, and was found in 3 women and 3 m en among the patient's 7 siblings, 2 boys and 2 girls among the 8 children of the siblings, and one female Tsou (4.5%, 1/22) and one female Atayal (1. 4%, 1/70), The serum uric acid concentration among male HPRTTsou carriers i n the patient's family was significantly higher than among those who had at least one HPRT gene that did not have HPRT,ou. Conclusion. We found that the HPRTTsou gene variant is partially responsibl e for the hyperuricemia in an aboriginal population in Taiwan known for a h igh incidence of gout.