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Russian Journal of Genetics

, Volume 44, Issue 10, pp 1212–1218 | Cite as

Predicting a clinical/biochemical phenotype for PKU/MHP patients with PAH gene mutations

  • J. Kasnauskienė
  • L. Cimbalistienė
  • V. Kučinskas
Experimental Articles
  • 133 Downloads

Abstract

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.

Keywords

Phenylalanine Hydroxylase Molecular Genetic Testing R408W Mutation Restriction Enzyme Digestion Analysis Human Phenylalanine Hydroxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© MAIK Nauka 2008

Authors and Affiliations

  • J. Kasnauskienė
    • 1
  • L. Cimbalistienė
    • 1
  • V. Kučinskas
    • 1
  1. 1.Department of Human and Medical GeneticsVilnius UniversityVilniusLithuania

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