INVESTIGATION OF SIX COMMON MUTATIONS ON PHENYLALANINE HYDROXYLASE GENE IN PHENYLKETONURIA PATIENTS IN GUILAN PROVINCE

Phenylketonuria (PKU) is an inborn error of amino acid metabolism that results
from a deficiency of phenylalanine hydroxylase (PAH). To date, more than 800 mutations have been
identified in the PAH gene and registered in the PAHdb database and the spectrum of these mutations
is varied in different populations. The main clinical manifestation of untreated patients is severe mental
retardation. The aim of the present study was to identify the frequency of six common mutations on
PAH gene in patients with PKU in Guilan province including p. R261Q, p. R252W, p.R261X, p.
E280Kp.R243X, and p.P281L.
Materials &Methods: In this descriptive cross-sectional study, 25 unrelated PKU patients (1 to 21 years
old, both female and male) in Guilan province were enrolled during a one-year period. Genomic DNA
was extracted from leukocytes using High Pure PCR Template Preparation kit (Roche) and polymerase
chain reaction. The sequencing method was applied to detect mutations.
Results: Two out of the six investigated mutations )p.R261Q, p.R252W, p.R261X, p.E280K, p.R243X,
and p.P281L(were identified among the patients. The p.R261X mutation had the highest frequency
(22%) among the patients and the frequency of p. R261Q mutation was 10%.
Conclusion: Although the present study investigated the frequencies of six mutations on the PAH gene,
the mutations were only found on 32% of the chromosomes. Hence, different mutations are responsible
for PKU disease in the north of Iran, and further studies are recommended to identify all of the mutations
on the PAH gene in the region.