Objective To describe mutation characteristics of the phenylalanine hydroxylase (PAH) gene in phenylketonuria (PKU) patients in Han ethnic group in Qinghai Province, in order to provide basic information for genetic counseling and prenatal diagnosis of PKU. Methods Mutations of the PAH were detected in promoter and exons 1-13 with flanking introns by PCR and DNA sequencing in 32 Han families with PKU. Results A total of 22 different mutations were detected in 55 out of 64 mutant alleles (85.9%), including 13 missense (59.1%), 5 nonsense (22.7%), 3 deletion (13.6%) and 1 splicing site (4.5%). Most mutations were detected in exons 3, 6, 7, 5, 11 and flaking introns. The most frequent mutations were p.R243Q (23.4%), IVS4-1G>A (10.9%), p.Y356X (9.4%) and p.EX6-96A>G (7.8%), followed by p.N93fsX5 (3.1%), p.R111X (3.1%), p.R400K (3.1%) and p.Q232X (3.1%). p.R243Q was the most prevalent mutation. Two novel mutations, p.N93fsX5 and p.G171E, were firstly identified in Han ethnic group and the p.H64fsX9 was the second documented in Chinese. Conclusion The mutation spectrum of PAH in Han ethnic group in Qinghai was similar to some Northern populations of China with obvious difference in mutation rate for some mutations. It suggests that p.R243Q, IVS4-1G>A, p.Y356X and p.EX6-96A>G are the hot spots of PAH mutations in Han ethnic group of Qinghai. p.N93fsX5, p.G171E and p.H64fsX9 are probably specific mutations of Han ethnic group in Qinghai Province, China.
Key words
Phenylketonuria /
Phenylalanine hydroxylase /
Mutation
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