HLA and hormonal data for identification of heterozygotes in 11 beta- and 17 alpha-hydroxylase deficiency syndromes.
1. In previous studies, baseline and ACTH-stimulated hormone levels, plus HLA genotyping, have been used to detect heterozygous carriers in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHDS). 2. In the present study similar parameters were determined in a family of four including two children with CAH due to 11 beta-hydroxylase deficiency (11-OHDS), and a family of twelve including three sibs (two females, one genotypically male) with CAH due to 17 alpha-hydroxylase deficiency (17-OHDS). 3. HLA typing showed affected sibs with 11-OHDS to differ in one of their haplotypes. No significant differences in basal and ACTH-stimulated steroid levels were seen between the parents (obligate heterozygotes) and the general population. 4. In 17-OHDS, affected members differed from one another in one to two haplotypes; one patient had identical HLA profiles with two of the normal siblings, as did the genotypically male patient with two others; each of the other healthy siblings had one haplotype found in two of the affected subjects. The genes responsible for 11-OHDS and 17-OHDS--in contrast with 21-OHDS--do not appear to be HLA-linked. However, the measurement of ACTH-stimulated corticosterone levels may be useful, since the gene responsible for 17-OHDS seems to be expressed hormonally in the heterozygous state.
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D006580:Genetic Carrier Screening; D006680:HLA Antigens / Q000032:analysis*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D013268:Stimulation, Chemical; D013577:Syndrome
D006680:HLA Antigens; D006728:Hormones; D000324:Adrenocorticotropic Hormone; D006899:Mixed Function Oxygenases