title: Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.
abstract: Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.
authors.affiliation: CEINGE-Biotecnologie Avanzate, scarl, Naples, Italy. salvator@unina.it
authors.forename: A
authors.initials: A
authors.lastname: Daniele
authors.forename: G
authors.initials: G
authors.lastname: Cardillo
authors.forename: C
authors.initials: C
authors.lastname: Pennino
authors.forename: M T
authors.initials: MT
authors.lastname: Carbone
authors.forename: D
authors.initials: D
authors.lastname: Scognamiglio
authors.forename: A
authors.initials: A
authors.lastname: Correra
authors.forename: A
authors.initials: A
authors.lastname: Pignero
authors.forename: G
authors.initials: G
authors.lastname: Castaldo
authors.forename: F
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D007558:Italy / Q000453:epidemiology; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation; D015997:Neonatal Screening; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000453:epidemiology / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D010651:Phenylalanine Hydroxylase