title: High frequency of nonclassical steroid 21-hydroxylase deficiency.
abstract: Nonclassical steroid 21-hydroxylase deficiency is an autosomal recessive disorder that is defined by clinical and hormonal criteria that distinguishes it from the classical 21-hydroxylase deficiency. No estimates of the gene frequency of nonclassical 21-hydroxylase deficiency, also called attenuated, late-onset, acquired, and cryptic adrenal hyperplasia, have been published thus far. Here, we have used HLA-B genotype data in families containing multiple members affected with nonclassical 21-hydroxylase deficiency together with the results of quantitative hormonal tests to arrive at estimates of gene and disease frequencies for this disorder. We found nonclassical 21-hydroxylase deficiency to be a far more common disorder than classical 21-hydroxylase deficiency, which occurs in 1/8,000 births. The prevalence of the disease in Ashkenazi Jews was 3.7%; in Hispanics, 1.9%; in Yugoslavs, 1.6%; in Italians, 0.3%; and in the diverse Caucasian population, 0.1%. The gene for nonclassical 21-hydroxylase deficiency is in genetic linkage disequilibrium with HLA-B14 in Ashkenazi Jews, Hispanics, and Italians, but not in Yugoslavs or in a diverse, non-Jewish, Caucasian group. The penetrance of nonclassical 21-hydroxylase deficiency gene in the HLA-B14 containing haplotypes was incomplete. Thus, nonclassical 21-hydroxylase deficiency is probably the most frequent autosomal recessive genetic disorder in man and is especially frequent in Ashkenazi Jews, Hispanics, Italians, and Yugoslavs.
authors.affiliation: Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Speiser
authors.forename: B
authors.initials: B
authors.lastname: Dupont
authors.forename: P
authors.initials: P
authors.lastname: Rubinstein
authors.forename: A
authors.initials: A
authors.lastname: Piazza
authors.forename: A
authors.initials: A
authors.lastname: Kastelan
authors.forename: M I
authors.initials: MI
authors.lastname: New
mesh_terms: D000312:Adrenal Hyperplasia, Congenital; D005787:Gene Frequency; D005808:Genes, Recessive; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D010375:Pedigree; D044469:Racial Groups; D012306:Risk
chemical_list: D015235:HLA-B Antigens