Molecular analysis of exon 6 mutations of phenylalanine hydroxylase gene in phenylketonuria patients from Guilan Province

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 disease in the Iranian population. Therefore, it is necessary to identify the disease-causing mutations in this population. According to the PAH database, one of the exons with the greatest number of mutant alleles is exon 6 and the surrounding introns. Accordingly, this study was designed to identify exon 6 mutations of PAH gene among PKU patients in Guilan province and compare them with studies conducted in other regions of Iran. In this descriptive cross-sectional study, 25 PKU patients and non-relatives (1 to 21 years old) from different regions of Guilan province were identified during a one-year period. After genomic DNA extraction, mutation detection was performed by polymerase chain reaction-sequencing method. The mutations and polymorphisms identified in this study included R176X (4%) and Q232Q (46%), respectively. The patient had mHPA phenotype and her parents were 3th degree relatives. Considering that the R176X mutation was only found in 4% of chromosomes in this study, achieving a complete spectrum of PAH gene mutations in PKU patients in Guilan province requires the analysis of 12 other exons. In addition, considering the difference of PAH mutation spectrum in different regions of Iran, comprehensive studies in different regions of Iran can identify specific mutations in each region and these studies can be used to advance the future preventive and therapeutic goals.