POLYMORPHIC DNA HAPLOTYPES AT THE PHENYLALANINE HYDROXYLASE LOCUS IN PRENATAL DIAGNOSIS OF PHENYLKETONURIA

Stephen P. Daiger, Ranajit Chakraborty, Flemming Güttler, Alan S. Lidsky, Richard Koch, Savio L.C. Woo

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Abstract

Restriction fragment length polymorphisms (RFLPs) detected in the human genome by means of a cDNA clone of phenylalanine hydroxylase (PAH) segregate concordantly with phenylketonuria (PKU) in several families. To establish the usefulness of these DNA polymorphisms for prenatal diagnosis of PKU the genotypes and chromosomal haplotypes of eight RFLPs at the PAH locus were determined in 46 families, each with one or more affected children. 34 of these families were informative for linkage analysis, giving a maximum probability of 109:1 in favour of tight linkage between PKU and the PAH RFLP haplotypes. Thus the deficiency of hepatic PAH in PKU patients is caused by mutations in the PAH gene itself, and the RFLPs could be used effectively for prenatal diagnosis and carrier detection of PKU in affected families. Use of the PKU haplotypes based on these eight RFLPs would establish disease status in approximately 87% of siblings at risk, although three RFLPs alone (detected with the restriction enzymes Pvu II, Xmn I, and EcoR R) are nearly as effective.

Original languageEnglish
Pages (from-to)229-232
Number of pages4
JournalThe Lancet
Volume327
Issue number8475
DOIs
StatePublished - 1 Feb 1986

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