Late onset 21-hydroxylase deficiency and HLA in the Ashkenazi population: A new Allele at the 21-hydroxylase locus

Z. Laron, M. S. Pollack, R. Zamir, A. Roitman, Z. Dickerman, L. S. Levine, F. Lorenzen, G. J. O'Neill, S. Pang, M. I. New, B. Dupont

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


The congenital form of 21-hydroxylase deficiency (21-OH-def), which results in virilization at birth from intrauterine exposure to testosterone, results from the inheritance of an HLA-linked recessive disease allele from each parent a t the 21-OH locus (the 21-OH0 allele). In this study we establish a relationship between intermediate and late onset 21-OH-def and HLA. In studies of five Ashkenazi families, we concluded that these syndromes can be caused by either of two combinations of genes at the 21-OH locus: They can occur in individuals who carry the 21-OH0 allele on one baplotype and who in addition inherit a "susceptibility" 21-OH-def gene (21-OH8) from their other parent (genotype = 21-OH0/21-OH3; or they can occur in individuals who are homozygous for the "susceptibility" 21-OH-def allele (21-OH8/21-OH3). The biochemical abnormality in late onset 21-OH-deficiency is characterized by elevated basline levels of plasma 17-hydroxyprogesterone (17-OH-P) and urinary pregnanetriol and/or relatively high 17-OH-P following ACTH stimulation. Although clinical symptoms are not always present in all family members with this biochemical abnormality, the abnormality appears to behave as a simple autosomal recessive trait that is linked to HLA. Among the five probands studied, eight of the eight haplotypes from five nonconsaguinous families assumed to carry the 21-OH3 allele had the HLA antigens B14 and DRwl and also had the factor B (Bf) S (Slow) variant. The two remaining disease haplotypes were assumed from biochemical data to carry 21-OH0 alleles. The results suggest that the biochemical abnormality in these syndromes is linked to HLA and that the 21-OH3 allele has nonrandom association with the particular HLA haplotype B14, DRwl, BfS in the Ashkenazi population.

Original languageEnglish (US)
Pages (from-to)55-66
Number of pages12
JournalHuman Immunology
Issue number1
StatePublished - Jul 1980
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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