Aim: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. To date there have been no reports on the molecular analysis of phenylketonuria in the Iranian Azeri Turkish population. In this study, a total of 88 independent alleles from this ethnic group were investigated.
Results: Thirteen different mutations have been detected, which account for 75% of the total mutant alleles. Two mutations were found at high frequencies: IVS10-11G>A (19.3%) and P281L (19.3%), possibly due to consanguinity and genetic drift, among other factors. The frequencies of the other mutations were c.590_612del (5.7%), R261Q (5.7%), R261X (4.5%), R243X (4.5%), IVS2+5G>C (3.4%), IVS4+1G>A (3.4%), R158Q (2.3%), E280K (2.3%), G247D (2.3%), IVS11+1G>C (1.1%), and R270K (1.1%).
Conclusions: These intriguing preliminary findings confirm IVS10-11G>A as a major mutation among Mediterranean mutations. For this population, exons 7 and 11 and adjacent introns, which carry more than 75% of the mutations, would have to be primarily screened. However, the other exons must be studied when either one or no mutations are found in the primary screening. The mutation spectrum in the patients with Azeri Turkish ethnic origin differed from that observed in patients from other Mediterranean countries and further defined the molecular heterogeneity of this disease.