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. 1990 Dec;47(6):1002–1007.

A termination mutant prevalent in Norwegian haplotype 7 phenylketonuria genes.

J Apold 1, H G Eiken 1, E Odland 1, A Fredriksen 1, A Bakken 1, J B Lorens 1, H Boman 1
PMCID: PMC1683913  PMID: 1978553

Abstract

RFLPs in the phenylalanine hydroxylase (PAH) gene locus were determined in 47 Norwegian nuclear families that had at least one child with phenylketonuria (PKU). The PKU haplotype distribution differed somewhat from that of other European populations. Mutant haplotype 7 is relatively rare in other populations but constituted 20% of all mutant haplotypes in Norway. In 14 of the 17 mutant haplotypes 7, a previously unreported deletion of the BamHI restriction site in exon 7 of the PAH gene was observed. The abrogation of the BamHI site was shown to be due to a G-to-T transversion, changing Gly 272 to Ter 272 in exon 7 of the gene, thus directly identifying the PKU mutation. Unlike the families of the other PKU patients, the families with this mutation clustered along the southeastern coast of Norway, suggesting a founder effect for this mutation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abadie V., Lyonnet S., Maurin N., Berthelon M., Caillaud C., Giraud F., Mattei J. F., Rey J., Rey F., Munnich A. CpG dinucleotides are mutation hot spots in phenylketonuria. Genomics. 1989 Nov;5(4):936–939. doi: 10.1016/0888-7543(89)90137-7. [DOI] [PubMed] [Google Scholar]
  2. Avigad S., Cohen B. E., Bauer S., Schwartz G., Frydman M., Woo S. L., Niny Y., Shiloh Y. A single origin of phenylketonuria in Yemenite Jews. Nature. 1990 Mar 8;344(6262):168–170. doi: 10.1038/344168a0. [DOI] [PubMed] [Google Scholar]
  3. Chakraborty R., Lidsky A. S., Daiger S. P., Güttler F., Sullivan S., Dilella A. G., Woo S. L. Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria. Hum Genet. 1987 May;76(1):40–46. doi: 10.1007/BF00283048. [DOI] [PubMed] [Google Scholar]
  4. DiLella A. G., Kwok S. C., Ledley F. D., Marvit J., Woo S. L. Molecular structure and polymorphic map of the human phenylalanine hydroxylase gene. Biochemistry. 1986 Feb 25;25(4):743–749. doi: 10.1021/bi00352a001. [DOI] [PubMed] [Google Scholar]
  5. DiLella A. G., Marvit J., Brayton K., Woo S. L. An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. 1987 May 28-Jun 3Nature. 327(6120):333–336. doi: 10.1038/327333a0. [DOI] [PubMed] [Google Scholar]
  6. DiLella A. G., Marvit J., Lidsky A. S., Güttler F., Woo S. L. Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria. 1986 Aug 28-Sep 3Nature. 322(6082):799–803. doi: 10.1038/322799a0. [DOI] [PubMed] [Google Scholar]
  7. Dworniczak B., Aulehla-Scholz C., Horst J. Phenylketonuria: detection of a frequent haplotype 4 allele mutation. Hum Genet. 1989 Dec;84(1):95–96. doi: 10.1007/BF00210683. [DOI] [PubMed] [Google Scholar]
  8. Gyllensten U. B., Erlich H. A. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7652–7656. doi: 10.1073/pnas.85.20.7652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. John S. W., Rozen R., Laframboise R., Laberge C., Scriver C. R. Novel PKU mutation on haplotype 2 in French-Canadians. Am J Hum Genet. 1989 Dec;45(6):905–909. [PMC free article] [PubMed] [Google Scholar]
  10. Kwok S. C., Ledley F. D., DiLella A. G., Robson K. J., Woo S. L. Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry. 1985 Jan 29;24(3):556–561. doi: 10.1021/bi00324a002. [DOI] [PubMed] [Google Scholar]
  11. Lichter-Konecki U., Konecki D. S., DiLella A. G., Brayton K., Marvit J., Hahn T. M., Trefz F. K., Woo S. L. Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene. Biochemistry. 1988 Apr 19;27(8):2881–2885. doi: 10.1021/bi00408a032. [DOI] [PubMed] [Google Scholar]
  12. Lyonnet S., Caillaud C., Rey F., Berthelon M., Frézal J., Rey J., Munnich A. Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency. Am J Hum Genet. 1989 Apr;44(4):511–517. [PMC free article] [PubMed] [Google Scholar]
  13. Okano Y., Wang T., Eisensmith R. C., Steinmann B., Gitzelmann R., Woo S. L. Missense mutations associated with RFLP haplotypes 1 and 4 of the human phenylalanine hydroxylase gene. Am J Hum Genet. 1990 Jan;46(1):18–25. [PMC free article] [PubMed] [Google Scholar]
  14. Saiki R. K., Bugawan T. L., Horn G. T., Mullis K. B., Erlich H. A. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature. 1986 Nov 13;324(6093):163–166. doi: 10.1038/324163a0. [DOI] [PubMed] [Google Scholar]
  15. Saugstad L. F. Anthropological significance of phenylketonuria. Clin Genet. 1975 Jan;7(1):52–61. [PubMed] [Google Scholar]
  16. Sullivan S. E., Moore S. D., Connor J. M., King M., Cockburn F., Steinmann B., Gitzelmann R., Daiger S. P., Woo S. L. Haplotype distribution of the human phenylalanine hydroxylase locus in Scotland and Switzerland. Am J Hum Genet. 1989 May;44(5):652–659. [PMC free article] [PubMed] [Google Scholar]
  17. Vandenplas S., Wiid I., Grobler-Rabie A., Brebner K., Ricketts M., Wållis G., Bester A., Boyd C., Måthew C. Blot hybridisation analysis of genomic DNA. J Med Genet. 1984 Jun;21(3):164–172. doi: 10.1136/jmg.21.3.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang T., Okano Y., Eisensmith R., Huang S. Z., Zeng Y. T., Lo W. H., Woo S. L. Molecular genetics of phenylketonuria in Orientals: linkage disequilibrium between a termination mutation and haplotype 4 of the phenylalanine hydroxylase gene. Am J Hum Genet. 1989 Nov;45(5):675–680. [PMC free article] [PubMed] [Google Scholar]
  19. Woo S. L. Collation of RFLP haplotypes at the human phenylalanine hydroxylase (PAH) locus. Am J Hum Genet. 1988 Nov;43(5):781–783. [PMC free article] [PubMed] [Google Scholar]

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