Frequency of PAH mutations among classic Phenylketon Urea patients in Mazandaran and Golestan Provinces, north of Iran
Frequency of PAH mutations among classic Phenylketon Urea patients in Mazandaran and Golestan Provinces, north of Iran
Elahe Hosseini,1Mohammad Bagher Hashemi-Soteh,2,*
1. Novin Genetic diagnostic Laboratory, FarahAbad Boulevard, Sari, Mazandaran, Iran 2. Immunogenetic Research center, Molecular and Cell biology Research center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Introduction: Phenylketonuria (PKU) is the most common aminoacidopathy with an autosomal recessive inheritance pattern. A global PKU prevalence is estimated about 6.002 in 100,000 new born. In Iran, the prevalence of PKU is estimated about 1 in 4,698 and it shows an increasing trend from north (0.0015%) to south (0.02%) of the country. Untreated PKU causes mental retardation, microcephaly and seizure. PAH gene mutations located at chromosome 12q23 are responsible for the classical type of this disease. The spectrum of PAH mutations is varied in different ethnicities and different parts. The aim of this study was to investigate the frequency of PAH mutation in Mazandaran province, which could be useful for genetic counseling and prenatal diagnosis.
Methods: A total of 66 individuals from 33 families from two provinces (9 family from Golestan and 24 family from Mazandaran) from north of Iran participated in this study. After genomic DNA extraction, PAH gene analysis was carried out using DNA sequencing of both coding and non-coding regions by ABI 3130XL genetic analyzer.
Results: 26 different mutations were identified in PAH gene in this study. Four mutations including IVS10-11 (c.1066-11G>A), c.727C>T (p.Arg243X), c.898G>T (p.Ala300Ser) and c.601C>T (p.His201Tyr) were the most common mutations with 37.48% frequency in Mazandaran province. Most frequent mutations in Golestan province were IVSI0-11 (c.1066-11G>A), c.722delG (p.Arg241fs), c.842C>T (p.Pro281Leu) and IVSII+5 (G>A) with frequency 58.57 % respectively
Conclusion: The results from present study verify heterogeneity of the PAH gene and may help to diagnosis tests for carrier detection and prenatal diagnosis of the PKU disease in Iranian population.