The spectrum of phenylketonuria genotypes in the Armenian population: identification of three novel mutant PAH alleles.

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.

• Authors: Natella Kostandyan, Corinne Britschgi, Albert Matevosyan, Alvina Oganezova, Anahit Davtyan, Nenad Blau, Beat Steinmann, Beat Thöny
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 104 Suppl Pg. S93-6 ( 2011) ISSN: 1096-7206 [Electronic] United States
• PMID: 21890392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Mutant Proteins
• Phenylalanine Hydroxylase

Topics

• Alleles
• Armenia
• Genotype
• Humans
• Mutant Proteins (genetics)
• Mutation (genetics)
• Phenylalanine Hydroxylase (genetics)
• Phenylketonurias (enzymology, genetics)