MOLECULAR-GENETICS OF PHENYLKETONURIA IN MEDITERRANEAN COUNTRIES - A MUTATION ASSOCIATED WITH PARTIAL PHENYLALANINE-HYDROXYLASE DEFICIENCY

  • 1 April 1989
    • journal article
    • research article
    • Vol. 44  (4) , 511-517
Abstract
We report the characterization of a mutation in the phenylalanine hydroxylase (PAH) gene associated wtih partial residual activity of the enzyme. This point mutation (280glu.fwdarw.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.fwdarw.lys) mutation is linked to and original an 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 Guthrei cards. Since a large number of patients can be screended 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.