A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients

Eur J Med Genet. 2019 Sep;62(9):103559. doi: 10.1016/j.ejmg.2018.10.011. Epub 2018 Oct 30.


Phenylketonuria (PKU) is a metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene. After thalassemia, PKU is considered as the most common autosomal recessive diseases in the Iranian population. Therefore, an efficient diagnostic strategy is required to identify disease-causing mutations in this population. Following our first report in 2003, here we presented a comprehensive study on the mutation spectrum of the PAH gene in the Iranian population. This study was performed on 280 unrelated chromosomes from 140 Iranian patients with classic PKU. All 13 exons as well as exon-intron boundaries of the PAH gene were analyzed by direct DNA sequencing. Thirty four different mutations were identified by a mutation detection rate of 100%. IVS10-11G > A, p.P281L, R261Q, p.F39del and IVS11+1G > C were the most prevalent mutations with frequencies of 26.07%, 19.3%, 12.86%, 6.07 and 3.93%, respectively. All other mutations represented a relative frequency less than 3.5%. The data from this study provided a comprehensive spectrum of the PAH gene mutations which can facilitate carrier detection and prenatal diagnosis of PKU disease in the Iranian population.

Keywords: Iranian population; Mutation analysis; Phenyalanine hydroxylase; Phenylketonuria.

MeSH terms

  • Gene Frequency*
  • Humans
  • Iran
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / epidemiology
  • Phenylketonurias / genetics*


  • Phenylalanine Hydroxylase