Mutations of the phenylalanine hydroxylase gene in Iranian patients with phenylketonuria.

Alireza Biglari,Mehdi Sahmani,Zahra Rashvand,Fatemeh Saffari,Safarali Alizadeh,Reza Najafipour

doi:10.1186/s40064-015-1309-8

Alireza Biglari, Mehdi Sahmani + Show 4 more

Open Access

https://doi.org/10.1186/s40064-015-1309-8

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Abstract

Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene. The aim of this study was the identification of sixteen different mutations in Iranian patients with hyperphenylalaninemia. The mutations were detected during the characterization of PAH genotypes of 39 PKU patients from Qazvin and Zanjan provinces of Iran. PAH mutations have been analyzed by PCR and direct sequencing of PCR products of the promoter region and all 13 exons of PAH gene, including the splicing sites. A mutation detection rate of 74.3 % was realized. Two mutations were found at high frequencies: R176X (10.25 %) and p.P281L (10.25 %). The frequencies of the other mutations were: IVS2+5G>A (2.56 %), IVS2+5G>C (2.56 %), p.L48S (2.56 %), p.R243Q (2.56 %), p.R252Q (5.12 %), p.R261Q (7.69 %), p.R261X (5.12 %), p.E280K (2.56 %), p.I283N (2.56 %), IVS9+5G>A (2.56 %), IVS9+1G>A (1.28 %), IVS11+1G>C (1.28 %), p.C357R (1.28 %), c.632delC (2.56 %). The present results confirm the high heterogeneity of the PAH locus and contribute to information about the distribution and frequency of PKU mutations in the Iranian population.

Highlights

Deficiency of hepatic phenylalanine hydroxylase (PAH) [EC.1.14.16.1], which converts phenylalanine to tyrosine, is the major frequent cause of hyperphenylalaninemia (Guldberg et al 1998)
The following polymorphisms were detected in the PAH gene: p.L385L, p.Q232Q and p.V245V with the frequency of 84, 51 and 17 % respectively were shown the highest prevalence among the other polymorphisms (Table 2)
Mutations p.R261X and Discussion In this study, we identified mutations in the PAH gene and to evaluate the genetic heterogeneity of PKU disease in 39 unrelated Iranian patients who had been referred to Qazvin and Zanjan provinces

Summary

Introduction

Deficiency of hepatic phenylalanine hydroxylase (PAH) [EC.1.14.16.1], which converts phenylalanine to tyrosine, is the major frequent cause of hyperphenylalaninemia (Guldberg et al 1998). This enzyme defect, causes toxic accumulation of phenylalanine in the body fluids and damage to the nervous system that can result in growth failure, microcephaly, mental retardation and neurobehavioral abnormalities (Zhang et al 2005). According the levels of phenylalanine, they are four categories: mild hyperphenylalaninemia (HPA), mild PKU, moderate-PKU, and classic-PKU. Classical PKU is the most severe form of this disorder. A phenylalanine restricted diet, can be Biglari et al SpringerPlus (2015) 4:542 analysis of a given population can be useful for the better understanding functional aspects of mutant protein and the relationship between genotype/phenotype

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