These authors equally contributed to this work.
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro
Article first published online: 7 JUL 2006
2006 Blackwell Munksgaard
Volume 70, Issue 2, pages 151–155, August 2006
How to Cite
Stojiljkovic, M., Jovanovic, J., Djordjevic, M., Grkovic, S., Cvorkov Drazic, M., Petrucev, B., Tosic, N., Karan Djurasevic, T., Stojanov, L. and Pavlovic, S. (2006), Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. Clinical Genetics, 70: 151–155. doi: 10.1111/j.1399-0004.2006.00650.x
- Issue published online: 7 JUL 2006
- Article first published online: 7 JUL 2006
- Received 10 March 2006, revised and accepted for publication 24 May 2006
- genotype–phenotype correlation;
- mutation analysis;
- phenylalanine hydroxylase gene;
Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism in Caucasians. PKU is caused by mutations in the gene encoding phenylalanine hydroxylase (PAH) enzyme. Here, we report the spectrum and the frequency of mutations in the PAH gene and discuss genotype–phenotype correlation in 34 unrelated patients with PKU from Serbia and Montenegro. Using both polymerase chain reaction–restriction fragment length polymorphism and ‘broad-range’ denaturing-gradient gel electrophoresis/DNA sequencing analysis, 19 disease-causing mutations were identified, corresponding to mutation detection rate of 97%. The most frequent ones were L48S (21%), R408W (18%), P281L (9%), E390G (7%) and R261Q (6%), accounting for 60% of all mutant alleles. The genotype–phenotype correlation was studied in homozygous and functionally hemizygous patients. We found that the most frequent mutation, L48S, was exclusively associated with the classical (severe) PKU phenotype. The mutation E390G gave rise to mild PKU. For the mutation R261Q, patients had been recorded in two phenotype categories. Considering allele frequencies, PKU in Serbia and Montenegro is heterogeneous, reflecting numerous migrations over the Balkan Peninsula.