Abstract
A novel substitution has been characterized in the phenylalanine hydroxylase (PAH) gene that is linked exclusively to mutant haplotype 6, which is prevalent in southern Europe but rare in northern and eastern Europe. It is a G-to-A transition in intron 10, 11 bases from exon 11. This substitution creates an additional AG dinucleotide, which may serve as a cryptic splice acceptor site. Individuals who bear this substitution in the homozygous state have a severe PKU phenotype with pretreatment serum phenylalanine levels over 1200 µmol/liter. The frequency and distribution of this substitution among European populations suggests two possible founding populations, one being Middle Eastern and the other Roman. The use of this substitution as a marker to identify PKU chromosomes will be an invaluable aid to carrier screening and prenatal diagnosis in populations where mutant haplotype 6 is prevalent.
Similar content being viewed by others
Literature cited
Scriver, C.R., Kaufman, S., and Woo, S.L.C. (1988).Annu. Rev. Genet. 22301–321.
Scriver, C.R., Kaufman, S., and Woo, S.L.C. (1989). In, 6th ed., (eds.) Scriver, C.R., Beaudet, A., Sly, W., Valle, D. McGraw-Hill, New York, pp. 495–546.
Kwok, S.C.M., Ledley, F.D., DiLella, A.G., Robson, K.J.H., and Woo, S.L.C. (1985).Biochemistry 24556–561.
Ledley, F.D., Grennet, H.E., DiLella, A.G., Kwok, S.C.M., and Woo, S.L.C. (1985).Science 22877–79.
Woo, S.L.C., Lidsky, A.S., Güttler, F., Chandra, T., and Robson, K.J.H. (1983).Nature 306151–155.
Lidsky, A.S., Ledley, F.D., DiLella, A.G., Kwok, S.C.M., Daiger, S.P., Robson, K.J.H., and Woo, S.L.C. (1985).Am. J. Hum. Genet. 37619–634.
DiLella, A.G., Kwok, S.C.M., Ledley, F.D., Marvit, J., and Woo, S.L.C. (1986).Biochemistry 25743–749.
Lidsky, A.S., Güttler, F., and Woo, S.L.C., (1985).Lancet 1549–551.
Ledley, F.D., Koch, R., Jew, K., Beaudet, A., O'Brien, W.E., Bartos, D.P., and Woo, S.L.C. (1988).Eur. J. Pediatr. 113463–468.
Wang, T., Okano, Y., Eisensmith, R.C., Fekete, G., Schuler, D., Berencsi, G., Nasz, I., and Woo, S.L.C. (1990).Somat. Cell Mol. Genet. 1685–89.
DiLella, A.G., Huang, W.M., and Woo, S.L.C. (1988).Lancet 1497–599.
Okano, Y., Eisensmith, R.C., Dasovich, M., Wang, T., Güttler, F., and Woo, S.L.C., (1990).Eur. J. Pediatr. (in press).
Shapiro, M.B., and Senapathy, P. (1987).NAR 157155–7174.
Weatherall, D.J., Clegg, J.B., Higgs, D.R., and Wood, W.G. (1989). In ??, 6th ed., (eds.) Scriver, C.R., Beaudet, A., Sly, W., Valle, D. (McGraw-Hill, New York), Chapter 93.
Morales, G., Requena, G.M., Jimenez-Ruiz, A., Lopez, M.C., Ugarte, M., and Alonso, C. (1990).Gene 93213–219.
Menozzi, P., Piazza, A., and Cavalli-Sforza, L. (1978).Science 201786–792.
Kalaydjieva, L., Dworniczak, B., Aulehla-Scholz, C., Kremensky, I., Bronzova, J., Eigel, A., and Horst, J. (1990).J. Med. Genet. 27742–745.
Özalp, I., Coskun, T., Ceyhan, M., Tokol, S., Oran, O., Erdem, G., Tekinalp, G., Durmus, Z., and Tarikahya, Y. (1986).J. Inher. Metab. Dis. 9(Suppl 2):237–239.
Ulusoy, M., and Tunçbilek, E. (1987).Turk. J. Popul. Stud. 97–26.
Williamson, M.L., Koch, R., Azen, C., and Chang, C. (1981).Pediatrics 68161–167.
Koch, R., Azen, C., Friedman, E.G., and Williamson, M.L. (1984).J. Inher. Metab. Dis. 786–90.
Özalp, I., Coskun, T., Tokol, S., Demicron, G., and Mönch, -. (1990).J. Inher. Metab. Dis. 13732–738.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dasovich, M., Konecki, D., Lichter-Konecki, U. et al. Molecular characterization of PKU allele prevalent in southern Europe and Ireland. Somat Cell Mol Genet 17, 303–309 (1991). https://doi.org/10.1007/BF01232824
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01232824