Abstract

We present the spectrum of phenylalanine hydroxylase (PAH) gene mutations upon investigating 35 index patients identified with hyperphenylalaninemia in Armenia. One patient was diagnosed with dihydropteridine reductase (DHPR) deficiency, whereas all other 34 and their 6 affected siblings presented with mild or classical phenylketonuria (PKU). By analyzing all 13 exons plus exon-intron boundaries of the PAH gene, we identified two mutant alleles in 23 PKU patients, three mutations in 1, only one mutation in 5, and no mutation in 5 PKU patients. The most prevalent mutation was the well defined splicing error in intron 10, c.1066-11G>A (17/68 alleles). The three alterations, c.836C>T (p.Pro279Leu) in exon 7, c.1129T>G (p.Tyr377Asp) in exon 11, and c.1244A>T (p.Asp415Val) in exon 12, have not been reported in the PAH locus database (http://www.pahdb.mcgill.ca) and, thus, might be specific for the culturally homogenous Armenian population.