Title: DETECTION OF E280K MUTATION AND ITS ASSOCIATION WITH VNTR IN PKU LIBYAN PATIENTS
Author(s): Nafisah Bakhit, Ahmed Atia and Abdulla Bashein
Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism caused by phenylalanine hydroxylase (PAH) deficiency. In the Eastern Mediterranean and North Africa region, C.1055del.G and E280K mutations in PAH gene are one of the most frequent mutations observed in PKU patients. The aim of this study was the identification of E280K mutation and its association with the VNTR in PKU Libyan patients. The study included twenty PKU patients from two Libyan families detected by newborn screening program from February to August 2014. Plasma amino acid analyses for all patients exhibited excess phenylalanine and little tyrosine levels consistent with the diagnosis of PKU. PAH mutation was detected by genomic DNA extraction from blood samples of PKU patients from Gharian and Misurata cities in Libya, and analyzed by direct sequencing of PCR products of the promoter region and 7 exon region of PAH gene. One confirmed positive PKU child from Gharian hospital (mutant E280K/E280K), with their parents were carried (E280K/ wild type) and their relatives were mixed (wild type and carriers). While in Misurata hospital, two PKU children detected and their parents were carriers (E280K/wild type).The distribution of E280K mutation in this study were 15% mutant, 55% carriers, and 30% wild type. VNTR units were observed in the affected children, and was associated with affected alleles in both families. The results suggest that VNTR can be used as a marker for the presence of E280K mutation in the studied population.