First Report of Variable Number of Tandem Repeat Alleles in Phenylalanine Hydroxylase Gene in Patients With Phenylketonuria From Guilan Province, Iran

Mutations in the phenylalanine hydroxylase (PAH) gene are the main reason for phenylketonuria (PKU). The multiplicity of mutations in the PAH gene, which leads to PKU, makes the diagnosis of pathogenic mutations impossible in many cases. In these cases, polymorphic markers in the PAH gene, such as the variable number of tandem repeats (VNTR) are used to determine the carriers in PKU families. This study aims to investigate the allele frequency of this marker in the PKU population of Guilan Province, Iran.

During one year, 25 unrelated PKU patients were identified from different areas of Guilan Province. After extracting DNA from patients’ blood, VNTR containing fragments of the PAH gene were assessed using the polymerase chain reaction (PCR)-sequencing method.

PCR products related to PAH VNTR alleles produced 380, 500, and 530 base pairs fragments. They were related to 3, 7, and 8 copies of the repeat units, respectively. In addition, these repetitions had a frequency of 6(12%), 6(12%), and 33(66%), respectively. Also, this study demonstrated that PKU patients in Guilan Province, Iran had VNTR3/VNTR3, VNTR3/VNTR8, ND/VNTR8, VNTR7/VNTR7, VNTR8/VNTR8, and ND/ND genotypes in the PAH gene.

This study is the first report on the genetic structure of the PKU population using PAH VNTR alleles in Guilan Province, Iran. Given the population diversity in Iran, it is necessary to study the frequency and distribution of VNTR alleles in different parts of the country.