JIMD Reports, Volume 42

V. Hamilton, L. Santa María, K. Fuenzalida, P. Morales, L.R. Desviat, M. Ugarte, B. Pérez, J.F. Cabello, V. Cornejo, L. R. Desviat, J. F. Cabello, Hamilton, V., Santa María, L., Fuenzalida, K., Morales, P., Desviat, L. R., Ugarte, M., Pérez, B., Cabello, J. F., Cornejo, V.

Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive disease, caused by mutations in the Phenylalanine Hydroxylase (PAH) gene situated in chromosome 12q22-q24.2. This gene has 13 exons. To date, 991 mutations have been described. The genotype is one of the main factors that determine the phenotype of this disease. Characterize PKU genotype and phenotype seen in Chilean PKU patients. We studied the PAH gene by restriction fragment length polymorphism (RFLP) and/or sequencing techniques to identify pathogenic mutations in 71 PKU subjects. We classified the phenotype according to Guldberg predicted value. We identified 26 different mutations in 134 of the 142 alleles studied (94.4%), 88.7% of the subjects had biallelic pathogenic mutations while 11.3% had only one pathogenic mutation identified. Compound heterozygous represented 85.9% of the cases. Exon 7 included the majority of mutations (26.9%) and 50% of mutations were missense. The most frequent mutations were c.1066-11G > A, c.442-?_509+?del and p.Val388Met. The majority of subjects (52.3%) had the classic phenotype. The most frequent mutations in our Chilean PKU population were p.Val388Met, c.442?_509+?del and c.1066-11G > A. It is possible to predict phenotype by detecting the genotype, and use this information to determine disease prognosis and adjust patient's medical and nutritional management accordingly.