RFLP DISCORDANCE IN A PKU FAMILY DUE TO A DELETION IN THE PAH GENE

We have previously reported preliminary data on a PKU family showing a discordant segregation of Pvu II (b) alleles at the PAH locus. A comb ination of several restriction enzymes and probe C2.6 (intron 2) as we ll as STR typing were used to dissect the molecular structure of the P AH gene around exon 3. In this family, the results of this analysis an d a re-examination of the physical map of the 5'-end of the gene provi ded strong evidence for the occurrence of a deletion removing exon 3, The ''Sicilian'' (approximately 2.5 kb) and ''Yemenite Jew'' (6.7 kb) deletions, the latter one also deleting exon 3, are different in terms of both the 5'-end breakpoint and apparent length. This study, beside s adding a new member to the long and increasing list of nearly 200 PA H gene mutations, also proposes to undertake a careful evaluation of R FLP discordances incidentally detected at the PAH locus.