Abstract
Phenylketonuria (PKU) is an inherited metabolic disease caused by recessively inherited mutations in the PAH gene that encodes the enzyme phenylalanine hydroxylase (PAH). Altogether, 20 diseases causing mutations were identified in Latvian PKU patients. R408W, the most common mutation, accounted for 73% of Latvian PKU chromosomes and was mostly observed in association with the VNTR3/STR238 minihaplotype. Minihaplotypes also were established for the other 19 mutations and one unknown PKU chromosome. Mutation E280K was almost exclusively associated with minihaplotype 9/250, and mutation IVS10-11G>A was strongly associated with the VNTR7/STR250 minihaplotype and was possibly of Mediterranean origin. It was found that minihaplotypes can be useful in studies concerning the origin and distribution of PAH mutations in human populations and for analysis of rare mutations in PAH gene and for prenatal diagnosis.