Mutation Spectrum of the Phenylalanine Hydroxylase Gene in Phenylketonuria Patients in Golestan Province, Iran

Abstract

Background. As an autosomal recessive disease, phenylketonuria (PKU) is caused by deficiency in phenylalanine hydroxylase (PAH) gene. The incidence of different mutations in phenylalanine hydroxylase is associated with differences in race and ethnicity. The aim of this study is to investigate the mutation spectrum in hotspot region of PAH gene in PKU patients. Materials and Method. For this purpose, we studied exons 6, 7, 10–11 and 12 and adjacent flanking regions of PAH gene from a total of 26 unrelated hyperphenylalaninemia patients (13 males and 13 females) in Golestan province using PCR-sequencing method. Results. Among 26 analyzed patients, 11 distinct mutations were found in combinations of 18 genotypes. A mutation detection rate of 64% was achieved. The high heterogeneity of PKU was reported in this study. The most prevalent mutations were IVS10-11G>A (19.23%), followed by IVS11+1G>C, p.P416HfsX36 and p.R261Q which accounted for 66.67% of mutant alleles. IVS9-1G>T and p.P416HfsX36 are novel mutations. Exonic polymorphisms L385L and Q232Q and intronic polymorphisms IVS10+155T>C, IVS10+156T>G, and IVS10-193G>C were found to have high frequency. Conclusion. A mutation spectrum with high frequency was predicted in Northern region of Iran due to its ethnic heterogeneity. Furthermore, it seems that the presence of some mutations in Golestan province indicates gene flow between Iran and the neighboring countries.