HAPLOTYPE ANALYSIS OF THE PHENYLALANINE HYDROXYLASE AND PRENATAL DIAGNOSIS OF PKU IN GERMANY

Abstract

Using a full-length cDNA clone for the human phenylalanine hydroxylase (PAH), haplotype analysis of the PAH genes was performed in (20) German PKU-families by determination of the restriction fragment length polymorphism (RFLP). As previously described for another population, an association between normal and mutant PAH-genes and certain haplotypes was observed. The analysis of 8 polymorphic sites detected by the restriction endonucleases revealed that 80% of the normal PAH genes were represented by 5 haplotypes among a possible total of 256 haplotypes. Four of these 5 haplotypes also accounted for greater than 90% of the PKU-genes studied. If each RFLP haplotype is associated with a specific mutation in the PAH gene that causes PKU, the data would suggest that PKU is a heterogeneous disease, and that a great majority of the PKU patients contain only a limited number of different mutant PAH genes in the German population. Indeed, specific RFLP haplotypes appear to be associated with particular disease phenotypes in a limited number of patients studied to date, such that it may be possible to predict the prognosis of disease from the haplotype data of the PKU-genes in the patients. Of 40 obligate carriers studied to date, a RFLP heterozygosity of 87.5% was observed. Since the restriction analysis can be readily performed using chromosomal DNA isolated from amniotic cells or chorionic villi, the data suggest that in 87.5% of the cases, prenatal diagnosis and carrier detection of PKU by gene analysis will be possible in Germany.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD