Phenylketonuria mutations in Europe.

Area of Science:

• Genetics
• Molecular Biology
• Population Genetics

Background:

• Phenylketonuria (PKU) is a genetically heterogeneous disorder.
• Over 400 distinct mutations in the phenylalanine hydroxylase (PAH) gene are known.
• Understanding regional mutation spectra is crucial for PKU management and research.

Purpose of the Study:

• To systematically review and identify prevalent PAH gene mutations in European PKU populations.
• To collate regional data on these mutations and analyze factors influencing their distribution.
• To assess the utility of molecular data for understanding PKU's clinical and population genetics.

Main Methods:

• Systematic literature review of molecular genetics studies on PKU in Europe.
• Identification and collation of data for 29 prevalent PAH mutations.
• Analysis of factors such as founder effect, migration, and genetic drift.

Main Results:

• Twenty-nine PAH mutations were identified as prevalent across European populations.
• Specific common mutations were noted in different regions (e.g., R408W in Eastern Europe and British Isles, IVS10-11G>A in the Mediterranean).
• Regional mutation spectra are shaped by founder effects, migration, and genetic drift.

Conclusions:

• The study provides a comprehensive overview of prevalent PAH mutations in Europe.
• Understanding these mutations aids in comprehending PKU's clinical variability and population genetics.
• Further data is needed to calculate relative allele frequencies for mild hyperphenylalaninemia (MHP).