Analysis of the phenylalanine hydroxylase gene in the Spanish population : Mutation profile and association with intragenic polymorphic markers

• Published in: American journal of human genetics Vol. 60; no. 1; pp. 95 - 102
• Main Authors: PEREZ, B, DESVIAT, L. R, UGARTE, M
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 1997
• Subjects: Aminoacid disorders; Biological and medical sciences; DNA Mutational Analysis; Electrophoresis; Errors of metabolism; Ethnic Groups - genetics; Gene Frequency; Genetic Heterogeneity; Genetic Markers; Haplotypes; Humans; Medical sciences; Metabolic diseases; Mutation; Phenylalanine Hydroxylase - genetics; Phenylketonurias - enzymology; Phenylketonurias - genetics; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Repetitive Sequences, Nucleic Acid; Spain; Europe; Spain; Human; Nervous system diseases; Phenylketonuria; Genetic inheritance; Phenylalanine 4-monooxygenase; Nucleotide sequence; Enzyme; Family study; Metabolic diseases; Tandemly repeated sequence; Enzymopathy; Epidemiology; Genetic disease; Allele; Restriction fragment length polymorphism; Genetics; Frequency; Oxidoreductases; Mutation; Aminoacid disorder
• ISSN: 0002-9297

The aim of this study was to characterize the phenylketonuria (PKU) alleles in the Spanish population, by both identifying the causative mutations and analyzing the RFLP haplotypes and the VNTR and short-tandem-repeat alleles associated with the phenylalanine hydroxylase (PAH) gene. We have investigated 129 independent mutant chromosomes, using denaturing gradient gel electrophoresis (DGGE) and direct sequencing. Ninety percent of the alleles were identified, and a total of 40 different mutations were detected. The mutational spectrum includes seven previously unreported mutations: P122Q, D129G, P147S, D151G, A165T, S196fs, and P407S. Seven mutations represent 43% of the Spanish PKU alleles, the most common being IVS10nt-11g-->a (14.7%), I65T (8.5%), and V388M (6.2%). The remaining 33 mutations are rare. The mutation profile and relative frequencies are markedly different from those in northern Europe, also showing unique features compared with those in other, southern European populations. The association analysis with polymorphic markers in the PAH gene provides valuable information for population-genetic studies and investigation of the origins of the mutations. This study may serve as reference in the analysis of the contemporary distributions and frequencies of the PKU mutations in related populations, with particular relevance in Latin American countries.