Genetic Mapping of the 21-Hydroxylase-Deficiency Gene within the HLA Linkage Group

Lenore S. Levine, Milo Zachmann, Maria I. New, Andrea Prader, Marilyn S. Pollack, Geoffrey J. O'neill, Soo Y. Yang, Sharon E. Oberfield, bo Dupont

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

To document further the proposed genetic linkage between congenital adrenal hyperplasia due to 21-hydroxylase deficiency and HLA, 34 unrelated families from New York and Zurich, with a total of 48 patients, 48 siblings and their parents, were studied. All patients were HLA genotypically different from the healthy sibs; when two or more children were affected in the same sibship they were always HLA-B identical. The gene for 21-hydroxylase deficiency was separated by genetic recombination from the HLA-A locus and from the locus for glyoxalase I-polymorphism. No HLA-A, HLA-B or HLA-C antigen was selectively increased among the 34 unrelated patients. Lod-score analysis for HLA-B:21-hydroxylase deficiency gave a peak for θ≈0.00 at 5.20 for females and 4.30 for males, giving a total peak lod score of 9.5 at θ≈0.00 when male and female lod scores were combined. Close genetic linkage between HLA-B and 21-hydroxylase deficiency was thus established. (N Engl J Med 299:911–915, 1978) CONGENITAL adrenal hyperplasia due to 21-hydroxylase deficiency is an inborn error of metabolism in which the hormonal pathophysiology is well defined.1 Early studies provided evidence that the disorder is transmitted by an autosomal recessive gene.2 3 4 We have recently presented preliminary evidence that congenital adrenal hyperplasia of the 21-hydroxylase-deficiency type is closely linked to HLA (the major histocompatibility complex of man).5 In this paper we report on studies of 34 unrelated families with a total of 48 patients. The studies demonstrate that the gene for congenital adrenal hyperplasia of the 21-hydroxylase-deficiency type is located very close to the HLA-B locus and.

Original languageEnglish (US)
Pages (from-to)911-915
Number of pages5
JournalNew England Journal of Medicine
Volume299
Issue number17
DOIs
StatePublished - Oct 26 1978
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Genetic Mapping of the 21-Hydroxylase-Deficiency Gene within the HLA Linkage Group'. Together they form a unique fingerprint.

Cite this