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. 1995 May;56(5):1034–1041.

Characterization of phenylalanine hydroxylase alleles in untreated phenylketonuria patients from Victoria, Australia: origin of alleles and haplotypes.

S J Ramus 1, E P Treacy 1, R G Cotton 1
PMCID: PMC1801443  PMID: 7726156

Abstract

Mutations in the phenylalanine hydroxylase (PAH) gene were identified in a group of untreated phenylketonuria patients from Victoria, Australia. Ninety-eight percent of the alleles were identified, and a total of 26 different mutations were detected on 83 independent chromosomes. The three most prevalent mutations--R408W, I65T, and IVS12nt1--together accounted for 54% of the alleles. A number of alleles were demonstrated, by genealogical studies, to be of Irish or Scottish origin, including a newly described mutation 1197/1198 del A. The distribution and relative frequencies of the more common alleles in this population parallel observed frequencies in the British Isles and are consistent with the known history of Caucasian settlement of this region of Australia. We have analyzed the haplotype and polymorphic short tandem-repeat allele of the mutant chromosomes and describe a number of new associations.

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Selected References

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

  1. Byck S., Morgan K., Tyfield L., Dworniczak B., Scriver C. R. Evidence for origin, by recurrent mutation, of the phenylalanine hydroxylase R408W mutation on two haplotypes in European and Quebec populations. Hum Mol Genet. 1994 Sep;3(9):1675–1677. doi: 10.1093/hmg/3.9.1675. [DOI] [PubMed] [Google Scholar]
  2. Dworniczak B., Wedemeyer N., Eigel A., Horst J. PCR detection of the PvuII (Ea) RFLP at the human phenylalanine hydroxylase (PAH) locus. Nucleic Acids Res. 1991 Apr 25;19(8):1958–1958. [PMC free article] [PubMed] [Google Scholar]
  3. Eiken H. G., Odland E., Boman H., Skjelkvåle L., Engebretsen L. F., Apold J. Application of natural and amplification created restriction sites for the diagnosis of PKU mutations. Nucleic Acids Res. 1991 Apr 11;19(7):1427–1430. doi: 10.1093/nar/19.7.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Eisensmith R. C., Woo S. L. Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus. Am J Hum Genet. 1992 Dec;51(6):1445–1448. [PMC free article] [PubMed] [Google Scholar]
  6. Forrest S. M., Dahl H. H., Howells D. W., Dianzani I., Cotton R. G. Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. Am J Hum Genet. 1991 Jul;49(1):175–183. [PMC free article] [PubMed] [Google Scholar]
  7. Goltsov A. A., Eisensmith R. C., Konecki D. S., Lichter-Konecki U., Woo S. L. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene. Am J Hum Genet. 1992 Sep;51(3):627–636. [PMC free article] [PubMed] [Google Scholar]
  8. Goltsov A. A., Eisensmith R. C., Naughton E. R., Jin L., Chakraborty R., Woo S. L. A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. Hum Mol Genet. 1993 May;2(5):577–581. doi: 10.1093/hmg/2.5.577. [DOI] [PubMed] [Google Scholar]
  9. Goltsov A. A., Eisensmith R. C., Woo S. L. Detection of the XmnI RFLP at the human PAH locus by PCR. Nucleic Acids Res. 1992 Feb 25;20(4):927–927. doi: 10.1093/nar/20.4.927-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jeffreys A. J., Royle N. J., Wilson V., Wong Z. Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature. 1988 Mar 17;332(6161):278–281. doi: 10.1038/332278a0. [DOI] [PubMed] [Google Scholar]
  11. Lidsky A. S., Ledley F. D., DiLella A. G., Kwok S. C., Daiger S. P., Robson K. J., Woo S. L. Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria. Am J Hum Genet. 1985 Jul;37(4):619–634. [PMC free article] [PubMed] [Google Scholar]
  12. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nelson P. V., Carey W. F., Morris C. P. Gene amplification directly from Guthrie blood spots. Lancet. 1990 Dec 8;336(8728):1451–1452. doi: 10.1016/0140-6736(90)93161-h. [DOI] [PubMed] [Google Scholar]
  14. Pitt D. B., Danks D. M. The natural history of untreated phenylketonuria over 20 years. J Paediatr Child Health. 1991 Jun;27(3):189–190. doi: 10.1111/j.1440-1754.1991.tb00384.x. [DOI] [PubMed] [Google Scholar]
  15. Pitt D. The natural history of untreated phenylketonuria. Med J Aust. 1971 Feb 13;1(7):378–383. doi: 10.5694/j.1326-5377.1971.tb87588.x. [DOI] [PubMed] [Google Scholar]
  16. Ramus S. J., Forrest S. M., Pitt D. B., Saleeba J. A., Cotton R. G. Comparison of genotype and intellectual phenotype in untreated PKU patients. J Med Genet. 1993 May;30(5):401–405. doi: 10.1136/jmg.30.5.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Svensson E., Eisensmith R. C., Dworniczak B., von Döbeln U., Hagenfeldt L., Horst J., Woo S. L. Two missense mutations causing mild hyperphenylalaninemia associated with DNA haplotype 12. Hum Mutat. 1992;1(2):129–137. doi: 10.1002/humu.1380010208. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Wedemeyer N., Dworniczak B., Horst J. PCR detection of the MspI (Aa) RFLP at the human phenylalanine hydroxylase (PAH) locus. Nucleic Acids Res. 1991 Apr 25;19(8):1959–1959. doi: 10.1093/nar/19.8.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]

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