title: Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria.
abstract: Taking advantage of the 'illegitimate' transcription of the phenylalanine hydroxylase (PAH) gene, we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes. Using this approach, we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients. One mutation, detected by the abnormal pattern of migration of an amplified fragment, is a C to T transition in the splice acceptor site of intron 10, which resulted in the skipping of exon 11 with the premature termination of RNA translation downstream from exon 12 (-3 IVS10). The other two mutations are missense mutations in exons 10 and 11 (respectively, L333F and E390G). The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U12, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Abadie
authors.forename: J
authors.initials: J
authors.lastname: Jaruzelska
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: P
authors.initials: P
authors.lastname: Millasseau
authors.forename: M
authors.initials: M
authors.lastname: Berthelon
authors.forename: F
authors.initials: F
authors.lastname: Rey
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J
authors.initials: J
authors.lastname: Rey
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005971:Glutamates; D018698:Glutamic Acid; D005998:Glycine; D006801:Humans; D007223:Infant; D007930:Leucine; D008099:Liver / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000201:enzymology* / Q000235:genetics*; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D014158:Transcription, Genetic
chemical_list: D003062:Codon; D005971:Glutamates; D009838:Oligodeoxyribonucleotides; D018698:Glutamic Acid; D010649:Phenylalanine; D004247:DNA; D010651:Phenylalanine Hydroxylase; D007930:Leucine; D005998:Glycine