Abstract
Congenital adrenal hyperplasia (CAH) due to 21-OHD has been found to be closely linked to the major histocompatibility complex (MHC) and more specifically to HLA-B. A two gene model, one on either side of HLA-D has however been suggested by several authors. We report studies in a CAH family suggesting that the (or one of the two) 21-OH gene might be centromeric to D. The index patient presented ambiguous genitalia (stage III) but no clinical salt loss ; diagnosis was delayed and progressive virilization developped : at 3 yr 4/12, pubic hair, accelerated growth and bone maturation (5 yr). Diagnostic levels (ng/dl) of testosterone (163) and 17α -OH-progesterone (OHP) (basal = 28690 - 114,910 after ACTH) were found. Elevated baseline levels (ng/dl/h) of PRA (1563) further rose after Na restriction (2880) or ACTH (4900). The 3 brothers were clinically normal. HLA typing revealed the first to be heterozygous, the 2nd homozygous normal ; the 3rd was found to be HLA identical and MLC identical to the CAH-sister (A2CW6 B57 DR6/AW30 CW2 BW47 DR2). Microlymphocytotoxicity tests excluded any recombination between the A and D loci. Hormonal studies (baseline and ACTH stimulated levels of OHP, progesterone and cortisol) showed a typical heterozygote response in both the mother and brother n° 3. Unfortunately, studies of the red cell glyoxalase I (GLO) were not informative. However, a DR-GLO recombination is the likely explanation for the present findings, suggesting a 21-OH locus between DR and GLO loci.
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Betuel, H., David, M., Guibaud, P. et al. HLA and congenital 21-hydroxylase (21-OHD) deficiency : further evidence for a 21-OH locus between DR and GLO. Pediatr Res 18, 1226 (1984). https://doi.org/10.1203/00006450-198411000-00151
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DOI: https://doi.org/10.1203/00006450-198411000-00151