Abstract
Phenylketonuria (PKU) is a monogenic autosomal recessive inherited metabolic disease. It is caused by mutation in the gene encoding enzyme phenylalaninhydroxylase (PAH).
The gene is located on the chromosome 12. It contains 13 exons and 8 polymorphic sites used for RFLP haplotype analysis.
Over 400 different mutations in PAH gene with different degrees of PAH enzyme impairment had been defined. There is a lot of possible mutation combinations with most of patients being compound heterozygotes rather than homozygotes for one particular allele.
This is the reason for excessive interindividual variability of metabolic phenotypes with continuous spectrum of mutation-related residual PAH activities. A strong correlation between PAH genotypes and its phenotypic outcome in most individuals was observed.
There is a strong linkage disequilibrium among PKU mutations and haplotypes together with other PAH gene polymorphisms. This provides a useful tool for studying population genetics of PKU.
We can confirm the descent of particular mutations and estimate their relative age. In the Czech PKU population, Kozák 1997 detected 30 different mutations, of which the most frequent was R408W in 54, 9% of all PKU alleles.
In the present, genotypic analysis is practically used mainly for prenatal diagnosis of PKU.