title: Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect.
abstract: The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.
authors.affiliation: Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: M
authors.initials: M
authors.lastname: Vela-Amieva
authors.affiliation: Programa de Maestría y Doctorado en Ciencias Biológicas, Facultad de Ciencias, Universidad Nacional Autónoma de México, México D.F., México.
authors.forename: M
authors.initials: M
authors.lastname: Abreu-González
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: A
authors.initials: A
authors.lastname: González-del Angel
authors.affiliation: Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas, UNAM - Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: I
authors.initials: I
authors.lastname: Ibarra-González
authors.affiliation: Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Lainez
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: R
authors.initials: R
authors.lastname: Barrientos-Ríos
authors.affiliation: Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: S
authors.initials: S
authors.lastname: Monroy-Santoyo
authors.affiliation: Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: S
authors.initials: S
authors.lastname: Guillén-López
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Secretaría de Salud, México.
authors.forename: M A
authors.initials: MA
authors.lastname: Alcántara-Ortigoza
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018703:Founder Effect; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008800:Mexico; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin
keywords: PKU; hyperphenylalaninemia; phenylketonuria; tetrahydrobiopterin