title: Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe.
abstract: Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hydroxylase (PAH) is the most common inborn error of amino acid metabolism. Clinically, the disorder is highly heterogeneous, spanning from nonphenylketonuria hyperphenylalaninemia to classical phenylketonuria. Only little is known about the molecular defects underlying hyperphenylalaninemia in Southern Europe. In this study, we conducted a systematic analysis of 53 patients from the Sicilian population. Each patient included in the study had persistently elevated blood levels of phenylalanine and met the differential criteria for PAH deficiency. Genomic DNA was analysed by scanning all PAH-coding exons for mutations by PCR in combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were completely genotyped. A spectrum of 40 different mutations was established including 17 novel PAH mutations. Our results explain the clinical heterogeneity of hyperphenylalaninemia in Southern Europe, and form the basis for the establishment of phenotype-genotype correlations in Sicily and surrounding countries.
authors.affiliation: Danish Center for Human Genome Research, John F. Kennedy Institute, Glostrup.
authors.forename: P
authors.initials: P
authors.lastname: Guldberg
authors.forename: V
authors.initials: V
authors.lastname: Romano
authors.forename: N
authors.initials: N
authors.lastname: Ceratto
authors.forename: P
authors.initials: P
authors.lastname: Bosco
authors.forename: M
authors.initials: M
authors.lastname: Ciuna
authors.forename: A
authors.initials: A
authors.lastname: Indelicato
authors.forename: F
authors.initials: F
authors.lastname: Mollica
authors.forename: C
authors.initials: C
authors.lastname: Meli
authors.forename: M
authors.initials: M
authors.lastname: Giovannini
authors.forename: E
authors.initials: E
authors.lastname: Riva
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010649:Phenylalanine / Q000097:blood*; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D012802:Sicily / Q000453:epidemiology
chemical_list: D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase