OBJECTIVE: To study the molecular basis of the phenylalanine hydroxylase (PAH) gene mutation in Chinese patients with phenylketonuria (PKU). METHODS: Using PCR/SSCP and DNA sequencing, we studied the mutations in exons 3, 5, 7, 10, 11, 12 of PAH gene. Totally 120 unrelated children with PKU and their parents from the northern region of China were included in the analysis. RESULT: Ten novel mutations were first time identified in Chinese PKU population as I65T, S70del, G239D, R241fsdelG, L255S, P281L, G346R, L367fsinsC, R400S and Ivsllnt2t-->c. The mutations G239D, R241fsdelG, R400S and Ivsllnt2t-->c have not been yet described in International PAH. In the present study we firstly identified the deletion, insertion and frameshift mutations of PAH gene in China PKU population. So far the mutant type of PAH gene in Chinese included: missense, nonsense, splice, silence, deletion, insertion and frameshift. Novel mutations mainly existed in exon 7: four in exon 7, two in exon 3, two in exon 11, one in exon 10 and one in intron 11. Each proportion of the ten novel mutations was very low (0.42%-1.3%). CONCLUSION: This study demonstrated the high heterogeneity of the PAH gene and the variety of the mutant type of Chinese PKU population and confirmed the exon 7 was the hot spot of PAH gene mutation.
OBJECTIVE: To study the molecular basis of the phenylalanine hydroxylase (PAH) gene mutation in Chinese patients with phenylketonuria (PKU). METHODS: Using PCR/SSCP and DNA sequencing, we studied the mutations in exons 3, 5, 7, 10, 11, 12 of PAH gene. Totally 120 unrelated children with PKU and their parents from the northern region of China were included in the analysis. RESULT: Ten novel mutations were first time identified in Chinese PKU population as I65T, S70del, G239D, R241fsdelG, L255S, P281L, G346R, L367fsinsC, R400S and Ivsllnt2t-->c. The mutations G239D, R241fsdelG, R400S and Ivsllnt2t-->c have not been yet described in International PAH. In the present study we firstly identified the deletion, insertion and frameshift mutations of PAH gene in China PKU population. So far the mutant type of PAH gene in Chinese included: missense, nonsense, splice, silence, deletion, insertion and frameshift. Novel mutations mainly existed in exon 7: four in exon 7, two in exon 3, two in exon 11, one in exon 10 and one in intron 11. Each proportion of the ten novel mutations was very low (0.42%-1.3%). CONCLUSION: This study demonstrated the high heterogeneity of the PAH gene and the variety of the mutant type of Chinese PKU population and confirmed the exon 7 was the hot spot of PAH gene mutation.