Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency

• Published in: American journal of human genetics Vol. 44; no. 4; pp. 511 - 517
• Main Authors: LYONNET, S, CAILLAUD, C, REY, F, BERTHELON, M, FREZAL, J, REY, J, MUNNICH, A
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.04.1989
• Subjects: Amino Acid Sequence; Aminoacid disorders; Base Sequence; Biological and medical sciences; Blotting, Northern; Errors of metabolism; Gene Amplification; Gene Frequency; Haplotypes; Humans; Medical sciences; Metabolic diseases; Mutation; Oligonucleotide Probes; Phenylalanine Hydroxylase - deficiency; Phenylalanine Hydroxylase - genetics; Phenylketonurias - genetics; Polymorphism, Restriction Fragment Length; Human; Molecular hybridization; Phenylketonuria; Nervous system diseases; Phenylalanine 4-monooxygenase; Enzyme; Family study; Metabolic diseases; Mediterranean Basin; Genetic disease; Restriction fragment length polymorphism; Enzymatic activity; Blotting assay; Point mutation; Polymérase chain reaction; Molecular probe; Southern blotting; Child; Aminoacid disorder
• ISSN: 0002-9297; 1537-6605

We report the characterization of a mutation in the phenylalanine hydroxylase (PAH) gene associated with partial residual activity of the enzyme. This point mutation (280glu---lys) was found by sequencing a mutant cDNA clone derived from a needle biopsy of the liver in a child with variant form of phenylketonuria. There is a strict concordance between homozygosity for the mutation and this particular phenotype. The (280glu---lys) mutation is linked to an original and rare RFLP haplotype at the PAH locus found in south Europe and North Africa. So far, this genotype-haplotype association is both inclusive and exclusive. Thirty-three PAH-deficient patients were screened for the mutation by using polymerase chain-reaction amplification of their genomic DNA extracted from Guthrie cards. Since a large number of patients can be screened for a particular mutation by using Guthrie cards, the possibility arises of using these samples collected by national newborn screening centers for prospective and retrospective detection of other mutations in the human genome.