title: Intra-familiar discordant PKU phenotype explained by mutation analysis in three pedigrees.
abstract: Classical phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are two phenotypes of phenylalanine hydroxylase (PAH) deficiency with different degrees of severity. We have analyzed three families in which classical PKU, MHP and a normal phenotype occurred within each family due to the different combinations of three mutations segregating within the family. Indeed, sequence PAH analysis revealed three different alleles segregating in each family. This report suggests that when discordant phenotypes occur in a family, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counseling and patient management. We further support the marked heterogeneity of hyperphenylalaninemia primarily due to allelic heterogeneity at the PAH locus.
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy. Electronic address: r.trunzo@unifg.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Trunzo
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Santacroce
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Longo
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Girolamo
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dimatteo
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Leccese
authors.affiliation: Ospedale Pediatrico "Giovanni XXIII", Bari, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Lillo
authors.affiliation: Ospedale Pediatrico "Giovanni XXIII", Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papadia
authors.affiliation: Genetica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*
chemical_list: D010651:Phenylalanine Hydroxylase
keywords: Discordant phenotypes; Gene PAH; Hyperphenylalaninemia