Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage

@article{Woolf1975PhenylketonuriaAA,
  title={Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage},
  author={L. Woolf and M. McBean and F. Woolf and S. Cahalanf},
  journal={Annals of Human Genetics},
  year={1975},
  volume={38}
}
Mothers of children with phenylketonuria have a significantly lower miscarriage rate than a matched control population in Ireland and west Scotland. This protective effect of the gene against some factor causing foetal death would seem to constitute a heterozygote advantage which might account for the previously observed polymorphism for phenylketonuria. It is suggested that the decrease in foetal mortality is mediated by the higher concentration of phenylalanine in the heterozygous mother's… Expand
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Phenylketonuria: A balanced polymorphism in Europe?
TLDR
Phenylketonuria is a highly deleterious recessive pathology of amino acid metabolism in which estimated allele frequencies may reach as high as 1·0 to 1·5% in some populations, and there may be, heterozygote advantage. Expand
Influence of the phenylketonuric heterozygote on the developing fetus
TLDR
Analysis of mental development scores in 82 non-PKU children age 3–14 years born to heterozygous mothers revealed normal values of psychometric tests. Expand
Heterozygote advantage for the phenylketonuria allele.
TLDR
Heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously-lethal allele by mutation alone. Expand
Heterozygote advantage for the phenylketonuria allele.
  • L. Saugstad
  • Biology, Medicine
  • Journal of medical genetics
  • 1978
TLDR
Heterozygote advantage presumably explains the presence of the allele at frequencies above those to be expected from the simple replacement of a homozygously-lethal allele by mutation alone. Expand
A role for overdominant selection in phenylketonuria? Evidence from molecular data
TLDR
Molecular genetic data generated over the last decade suggest that the concomitant excess of (unaffected) PKU carriers is at least in part the result of overdominant selection (“heterozygous advantage”). Expand
Effects of Untreated Maternal Phenylketonuria and Hyperphenylalaninemia on the Fetus
Abstract We studied the effects of maternal phenylketonuria and hyperphenylalaninemia on 53 offspring from untreated pregnancies in 22 mothers who were identified by routine screening of… Expand
Phenylketonuria from genetics to clinics: An Iranian prospect
TLDR
Clinical and molecular basis of the PKU disease, with emphasis on the studies performed in Iranian population, were reviewed and investigated toward the elucidation of molecular aspects of the disease. Expand
A method for analysing fertility of heterozygotes for autosomal recessive disorders, with special reference to cystic fibrosis, Tay‐Sachs disease and phenylketonuria
TLDR
A method has been developed which offers a better approach to the study of heterozygotes fertility in those autosomal recessive conditions which lack a test for direct heterozygote detection. Expand
A single origin of phenylketonuria in Yemenite Jews
TLDR
It is reported that a single molecular defect—a deletion spanning the third exon of the PAH gene—is responsible for all the PKU cases among the Yemenite Jews. Expand
Birth weight and pathogenesis in phenylketonuria.
TLDR
The results do not provide support for the "justification" hypothesis that the mental and neurological defects in phenylketonuria result from prenatal tyrosine deprivation which would be reflected in lower birthweights. Expand
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References

SHOWING 1-10 OF 44 REFERENCES
A third allele at the phenylalanine-hydroxylase locus in mild phenylketonuria (hyperphenylalaninaemia).
TLDR
It is suggested that the two unusual parents and their affected offspring possessed a variant form of phenylalanine hydroxylase strongly inhibited by excess phenyl Alanine and coded for by a third allele at the phenylAlanine-hydroxyl enzyme locus. Expand
Children of mothers with phenylketonuria.
TLDR
It is suggested that planned pregnancies and dietary restrictions during the fertile period and during any ensuing pregnancy is the only method of avoiding a high fetal environment of phenylalanine and its teratogenic effects. Expand
Maternal phenylketonuria: implications for growth and development.
TLDR
Growth data from these cases and additional previously unpublished growth data on 13 non-PKU offspring of 3 phenylketonuric mothers demonstrated uniform intrauterine and postnatal growth retardation. Expand
Causes for high phenylalanine with normal tyrosine in newborn screening programs.
TLDR
It is only recently that a critical appraisal of the value of a low-phenylalanine diet in preventing the mental defect in patients with phenylketonuria is getting a critical assessment. Expand
Genetics of Phenylketonuria: Heterozygosity for phenylketonuria
The first article deals with the problem of using the response to injected phenylalanine to determine whether or not the subject is heterozygous for phenylketonuria. The second article suggests a… Expand
CHILDREN OF MOTHERS WITH PHENYLKETONURIA.
TLDR
It is suggested that perhaps the level of phenylalanine and/or its intermediate metabolites in the maternal serum of a woman with phenylketonuria is the determining factor as to whether the offspring is retarded. Expand
Congenital malformations in offspring of phenylketonuric mothers.
TLDR
A family study has been presented in which two PKU females on non-restricted diets have had 16 abortions, 6 offspring who died in infancy, and 4 presently surviving children, and the presence of normal phenylalanine tolerance tests in the three children of the PKU mothers available for testing is found. Expand
The birthplaces of parents and grandparents of a series of patients with phenylketonuria in south‐east England
A comparison has been made of the birthplaces of the parents and grandparents of a series of patients with phenylketonuria with those of the parents and grandparents of three control series of… Expand
Phenylalanine-hydroxylase activity in hyperphenylalaninaemia.
TLDR
Phenylalanine-hydroxylase activities have been determined in two cases of " classic " phenylketonuria and in three cases of hyperphenylalaninaemia without phenyletonuria, which may constitute a clinical variant of phenyl ketonuria. Expand
Phenylketonuria. Mass screening of newborns in Ireland.
  • S. Cahalane
  • Medicine
  • Archives of disease in childhood
  • 1968
TLDR
It was decided to make the Guthrie method generally available, so that all newborn infants in the Republic of Ireland could be tested, and of the results achieved in the first 16 months of its operation, is given in this report. Expand
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