Hanieh Noferesti - Kawsar Human Genetics Research Center (KHGRC),Tehran,Iran
Zohreh Sharifi - Kawsar Human Genetics Research Center (KHGRC),Tehran,Iran
Tina Shirzad - Kawsar Human Genetics Research Center (KHGRC),Tehran,Iran
Marziyeh Mojbafan - Kawsar Human Genetics Research Center (KHGRC),Tehran,Iran

Phenylketonuria (PKU) is one of the most common in born error of metabolism of amino acid catabolism with autosomal recessive inheritance. Mainly the disease causation is located in the phenylalanine hydroxylase (PAH) gene. The gene is involved in breaking down of phenylalanine. PKU is mostly a curable disorder, so is crucial in patient management and can prevent disease consequences. Untreated individuals show different levels of mental and physical retardation. Genetic testing is not only necessary to confirm the clinical diagnosis but also helps prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for at risk families.Iran is a country with 38.4% consanguineous marriages. So, it is expected to have higher rate of autosomal recessive disorder. National newborn screening program of PKU has been in practice since 2007 in Iran. 4200 patients with clinical diagnosis of PKU were referred to Dr.Zeinali’s medical genetic laboratory since 2012.Direct sequencing of the PAH gene was performed using specific primers amplifying exons and the exon-intron boundaries in the affected children and results were confirmed by segregation analysis of the mutation(s) in the family.Initial investigation of the pedigrees revealed 403 cases with first cousin marriages. Among them, 19 patients were found to have a compound heterozygote mutation (4.7%). Totally 38 different types of mutations were found. Most of them were recurrent point mutations and rarely small deletions. So genetic testing confirmed the clinical diagnosis of PKU. According to the inheritance pattern of the disease and the close consanguinity of the parents, it is expected that just homozygote mutations can justify the disease causation. However, it seems that due to the Iranian population, it is possible to see compound heterozygous mutations even in first cousin marriages.

Phenylketonuria (PKU),metabolism,prenatal diagnosis (PND) ,preimplantation genetic diagnosis (PGD)