[Mutational analysis of patients with 6-pyruvoyltetrahydrobiopterin synthesis deficiency].

Objective To determine the gene mutation spectrum of patients with 6pyruvoyltetrahydrobiopterin synthesis deficiency (PTPSD) in Mainland China. Methods The 6pyruvoyltetrahydrobiopterin synthesis gene (PTS) was analyzed in 55 PTPSD patients by using PCRrestriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. The relationship between the genotype and phenotype was analyzed. Results Eighteen mutations were identified and the detection rate of gene mutation was 95.28%. Four hot-spot mutations, namely P87S(40.57%), N52S (13.21%), D96N(12.26%) and IVSInt-291A>G(10.38%) were found in this study, and the first three were associated with severe phenotype. The P87L was reported firstly in Chinese patients, and the Q13X, M80T, IVS4nt-2A>G, L93M and K131N were novel mutations. Conclusion The P87S, N52S, D96N and IVSInt-291A>G mutations are the hot-spots mutations of the PTS gene in Chinese PTPSD patients. Using PCR-RFLP technique to screen the mutations in the PTS gene can increase the efficiency of gene diagnosis. Key words: hyperphenylalaninemia;  tetrahydrobiopterin defieiency;  6-pyruvoyhe-trahydrobiopterin synthesis gene;  mutation