Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1994 Aug;55(2):321–326.

Mutation profiles of phenylketonuria in Quebec populations: evidence of stratification and novel mutations.

R Rozen 1, A Mascisch 1, M Lambert 1, R Laframboise 1, C R Scriver 1
PMCID: PMC1918360  PMID: 7913581

Abstract

Independent phenylketonuria (PKU) chromosomes (n = 109) representing 80% of a proband cohort in Quebec province carry 18 different identified mutations in 20 different mutation/haplotype combinations. The study reported here, the third in a series on Quebec populations, was done in the Montreal region and predominantly on French Canadians. It has identified three novel mutations (A309D, D338Y, and 1054/1055delG[352fs]) and one unusual mutation/RFLP haplotype combination (E280K on Hp 2). The relative frequencies and distribution of PKU mutations were then compared in three regions and population subsets (eastern Quebec, French Canadian; western Quebec, French Canadian; and Montreal, non-French Canadian). The distributions of the prevalent and rare mutations are nonrandom and provide evidence for genetic stratification. The latter and the presence of eight unusual mutation/haplotype combinations in Quebec families with European ancestries (the aforementioned four and M1V, I65T, S349P, and R408W on Hp 1) corroborate demographic and anthropologic evidence, from elsewhere, for different origins of French Canadians in eastern and western Quebec.

Full text

PDF
321

Images in this article

324Figure 1
on p.324

Selected References

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

  1. Bouchard G. Representations de la population et de la societe quebecoises: l'apprentissage de la diversite. Cah Que Demogr. 1990 Spring;19(1):7–28. [PubMed] [Google Scholar]
  2. De Braekeleer M., Dionne C., Gagné C., Julien P., Brun D., Ven Murthy M. R., Lupien P. J. Founder effect in familial hyperchylomicronemia among French Canadians of Quebec. Hum Hered. 1991;41(3):168–173. doi: 10.1159/000153996. [DOI] [PubMed] [Google Scholar]
  3. Dockhorn-Dworniczak B., Dworniczak B., Brömmelkamp L., Bülles J., Horst J., Böcker W. W. Non-isotopic detection of single strand conformation polymorphism (PCR-SSCP): a rapid and sensitive technique in diagnosis of phenylketonuria. Nucleic Acids Res. 1991 May 11;19(9):2500–2500. doi: 10.1093/nar/19.9.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Economou-Petersen E., Henriksen K. F., Guldberg P., Güttler F. Molecular basis for nonphenylketonuria hyperphenylalaninemia. Genomics. 1992 Sep;14(1):1–5. doi: 10.1016/s0888-7543(05)80274-5. [DOI] [PubMed] [Google Scholar]
  5. Eisensmith R. C., Okano Y., Dasovich M., Wang T., Güttler F., Lou H., Guldberg P., Lichter-Konecki U., Konecki D. S., Svensson E. Multiple origins for phenylketonuria in Europe. Am J Hum Genet. 1992 Dec;51(6):1355–1365. [PMC free article] [PubMed] [Google Scholar]
  6. Eisensmith R. C., Woo S. L. Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. Hum Mutat. 1992;1(1):13–23. doi: 10.1002/humu.1380010104. [DOI] [PubMed] [Google Scholar]
  7. Guldberg P., Henriksen K. F., Güttler F. Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics. 1993 Jul;17(1):141–146. doi: 10.1006/geno.1993.1295. [DOI] [PubMed] [Google Scholar]
  8. Guldberg P., Romano V., Ceratto N., Bosco P., Ciuna M., Indelicato A., Mollica F., Meli C., Giovannini M., Riva E. Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe. Hum Mol Genet. 1993 Oct;2(10):1703–1707. doi: 10.1093/hmg/2.10.1703. [DOI] [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. John S. W., Rozen R., Scriver C. R., Laframboise R., Laberge C. Recurrent mutation, gene conversion, or recombination at the human phenylalanine hydroxylase locus: evidence in French-Canadians and a catalog of mutations. Am J Hum Genet. 1990 May;46(5):970–974. [PMC free article] [PubMed] [Google Scholar]
  11. John S. W., Scriver C. R., Laframboise R., Rozen R. In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. Hum Mutat. 1992;1(2):147–153. doi: 10.1002/humu.1380010210. [DOI] [PubMed] [Google Scholar]
  12. Konecki D. S., Lichter-Konecki U. The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum Genet. 1991 Aug;87(4):377–388. doi: 10.1007/BF00197152. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Lyonnet S., Melle D., de Braekeleer M., Laframboise R., Rey F., John S. W., Berthelon M., Berthelot J., Journel H., Le Marec B. Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France. Am J Hum Genet. 1992 Jul;51(1):191–196. [PMC free article] [PubMed] [Google Scholar]
  15. Okano Y., Wang T., Eisensmith R. C., Güttler F., Woo S. L. Recurrent mutation in the human phenylalanine hydroxylase gene. Am J Hum Genet. 1990 May;46(5):919–924. [PMC free article] [PubMed] [Google Scholar]
  16. Pérez B., Desviat L. R., Die M., Ugarte M. Mutation analysis of phenylketonuria in Spain: prevalence of two Mediterranean mutations. Hum Genet. 1992 May;89(3):341–342. doi: 10.1007/BF00220555. [DOI] [PubMed] [Google Scholar]
  17. Treacy E., Byck S., Clow C., Scriver C. R. 'Celtic' phenylketonuria chromosomes found? Evidence in two regions of Quebec Province. Eur J Hum Genet. 1993;1(3):220–228. doi: 10.1159/000472415. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES