Objective: To understand the mutant spectrum of phenylalanine hydroxylase (PAH) gene in Northern Chinese.
Methods: All the exons and flaking introns of PAH gene were detected by PCR-single strand conformation polymorphism (PCR/SSCP) and sequencing in 230 patients with phenylketonuria (PKU).
Results: (1) A total of 75 different mutations were detected in 435 out of 460 mutant alleles (94.6%). Among them 3 mutations (S251-R252>SfsX89, Y387D and A389G) have not been reported previously. The mutations, R243Q, EX6-96A>G, R111X, R413P and Y356X, were the prevalent mutations with relative frequencies of 21.7%, 10.2%, 8.3%, 6.5%, and 6.1% respectively, followed by V399V(4.1%), IVS4-1G>A (3.5%), IVS7+2T>A (2.2%) and R241C(2.2%). Most mutations were detected in exons 3, 5, 6, 7, 11 and 12 and flaking introns of PAH gene. (2) Ten polymorphism sites were detected in the study. Four sites, IVS3-22C>T, IVS10+97G>A, Q232Q and V245V, had high relative frequencies of 56.7%, 75.9%, 89.0% and 81.9% respectively. It would suggest that the race diversity exists in PAH cDNA sequence.
Conclusion: The mutation spectrum of PAH gene in Northern Chinese is similar to other Asian populations but significantly different from European populations.