Predicting a clinical/biochemical phenotype for PKU/MHP patients with PAH gene mutations
- 133 Downloads
Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). In this study, a total of 218 independent PAH chromosomes (109 unrelated patients with PKU residing in Lithuania) were investigated. All 13 exons of the PAH gene of all PKU probands were scanned for DNA alterations by denaturing gradient gel electrophoresis (DGGE). In the cases of a specific DGGE pattern recognized, mutations were identified by direct fluorescent automated sequencing or by restriction enzyme digestion analysis of relevant exons. Twenty-five different PAH gene mutations were identified in Lithuania. We estimated a connection between individual PAH locus mutations and biochemical and metabolic phenotypes in patients in whom the mutant allele acts on its own, i.e., in functionally hemizygous patients and using the assigned value (AV) method to determine the severity of both common and rare mutant alleles, as well as to check a model to predict the combined phenotypic effect of two mutant PAH alleles.
KeywordsPhenylalanine Hydroxylase Molecular Genetic Testing R408W Mutation Restriction Enzyme Digestion Analysis Human Phenylalanine Hydroxylase
Unable to display preview. Download preview PDF.
- 1.Scriver, C.R., Kaufman, S., and Woo, S.L.C., The Phenylalaninemias, The Metabolic and Molecular Bases of Inherited Disease, Scriver, C.R., Beaudet, A.L., Valle. D., and Sly, W., New York: McGraw-Hill, 2001, pp. 15–1077.Google Scholar
- 7.Online Mendelian Inheritance in Man (OMIM), URL: http://www.ncbi.nlm.nih.gov/omim.
- 8.Scriver, C.R. and Nowacki, P.M., PAHdb: Phenylalanine Hydroxylase Locus Database, available from URL: http://www.mcgill.ca/pahdb, update, 1996.
- 9.Güttler, F., Hyperphenylalaninemia: Diagnosis and Classification of the Various Types of Phenylalanine Hydroxylase Deficiency, Acta Pediatr. Scand. Suppl., 1980, vol. 280, pp. 1–80.Google Scholar