title: Genetic analysis of treated and untreated phenylketonuria in one family.
abstract: We describe a family in which four subjects in two generations have a disorder of phenylalanine metabolism. Two first cousins had different biochemical presentations in the neonatal period. The older child was thought to have a more severe form of phenylketonuria (PKU), and the younger child a milder form. While carrying out family studies we discovered that their mutual grandfather and his older unmarried brother, both of normal intelligence, had a marked and previously undiagnosed hyperphenylalaninaemia. DNA analysis using RFLP haplotypes has shown that there are four independent mutant PKU alleles in this family which are found on three haplotype patterns. None of the affected family members carries a previously defined mutation at the phenylalanine hydroxylase (PAH) locus and so DNA analysis was not able to explain the apparently different biochemical phenotypes in the affected members of this family.
authors.affiliation: Department of Clinical Chemistry, Southmead Hospital, Westbury-on-Trym, Bristol.
authors.forename: L A
authors.initials: LA
authors.lastname: Tyfield
authors.forename: A L
authors.initials: AL
authors.lastname: Meredith
authors.forename: M J
authors.initials: MJ
authors.lastname: Osborn
authors.forename: R
authors.initials: R
authors.lastname: Primavesi
authors.forename: T L
authors.initials: TL
authors.lastname: Chambers
authors.forename: J B
authors.initials: JB
authors.lastname: Holton
authors.forename: P S
authors.initials: PS
authors.lastname: Harper
mesh_terms: D000293:Adolescent; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010649:Phenylalanine / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D014443:Tyrosine / Q000097:blood
chemical_list: D014443:Tyrosine; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase