OBJECTIVE: To study the mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene (PAH) in Shanxi population. METHODS: The mutations in exons 3, 6, 7, 11 and 12 and flanking sequences of PAH gene were detected by PCR-DNA sequencing, in 59 patients with phynelketonuria(PKU) and 100 healthy children from Shanxi province. RESULTS: By sequence analysis, three single nucleotide polymorphism (SNP) Q232Q (CAA>CAG), V245V (GTG>GTA) and L385L (CTG>CTC) were detected in both the patients and healthy children, with the frequencies of nt 696, 735 and 1155 of the PAH cDNA up to 96.2%, 76.1% and 7.6% in patients respectively, and 97.0%, 77.3% and 8.3% respectively in the healthy controls. In addition, 72 different mutations accounting for 61.0% of mutant alleles were identified in the patients only. In exon 3, R111X, H64>TfsX9 and S70 del were found accounting for 5.1%, 0.8% and 0.8%; EX6-96A>G in exon 6 was found accounting for 10.2%. In exon 7, R243Q was the highest incidence accounting for 12.7%, followed by Ivs7+2 T>A(5.1%) and T278I(2.5%); the lowest incidences were G247V, R252Q, L255S, R261Q and E280K accounting for 0.8 %, respectively. In exon 11, Y356X (5.9%) and V399V (5.1%) were found; in exon 12, R413P and A434D were found accounting for 5.9% and 2.5%. In total, 9 missense mutations, 3 splice site mutations, 2 nonsense mutations and 2 deletions were included in 16 kinds of different mutations. CONCLUSION: The mutation characteristics and distribution in exons 3, 6, 7, 11 and 12 of the PAH gene have been identified, and it suggested that the EX6-96A>G and R243Q were the hot spots of PAH gene mutations in Shanxi PKU population.
OBJECTIVE: To study the mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene (PAH) in Shanxi population. METHODS: The mutations in exons 3, 6, 7, 11 and 12 and flanking sequences of PAH gene were detected by PCR-DNA sequencing, in 59 patients with phynelketonuria(PKU) and 100 healthy children from Shanxi province. RESULTS: By sequence analysis, three single nucleotide polymorphism (SNP) Q232Q (CAA>CAG), V245V (GTG>GTA) and L385L (CTG>CTC) were detected in both the patients and healthy children, with the frequencies of nt 696, 735 and 1155 of the PAH cDNA up to 96.2%, 76.1% and 7.6% in patients respectively, and 97.0%, 77.3% and 8.3% respectively in the healthy controls. In addition, 72 different mutations accounting for 61.0% of mutant alleles were identified in the patients only. In exon 3, R111X, H64>TfsX9 and S70 del were found accounting for 5.1%, 0.8% and 0.8%; EX6-96A>G in exon 6 was found accounting for 10.2%. In exon 7, R243Q was the highest incidence accounting for 12.7%, followed by Ivs7+2 T>A(5.1%) and T278I(2.5%); the lowest incidences were G247V, R252Q, L255S, R261Q and E280K accounting for 0.8 %, respectively. In exon 11, Y356X (5.9%) and V399V (5.1%) were found; in exon 12, R413P and A434D were found accounting for 5.9% and 2.5%. In total, 9 missense mutations, 3 splice site mutations, 2 nonsense mutations and 2 deletions were included in 16 kinds of different mutations. CONCLUSION: The mutation characteristics and distribution in exons 3, 6, 7, 11 and 12 of the PAH gene have been identified, and it suggested that the EX6-96A>G and R243Q were the hot spots of PAH gene mutations in Shanxi PKU population.