Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia.
Serum androgens and 17-hydroxyprogesterone concentrations and HLA genotypes were determined in 124 families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). In 8 pedigrees, we discovered 16 pubertal or postpubertal family members of either sex who had biochemical evidence of 21-hydroxylase deficiency but were without clinical symptoms of excess virilism, amenorrhea, or infertility. We designated these family members as individuals with cryptic 21-hydroxylase deficiency. Within each generation, the family members with cryptic 21-hydroxylase deficiency were HLA identical. It is proposed that these family members are genetic compounds, having 21-hydroxylase deficiency as a result of two recessive gene defects: 1) a severe 21-hydroxylase gene defect present in the index case with classical CAH (21-OHCAH) and 2) a mild 21-hydroxylase gene defect (21-OHCRYPTIC). Thus, the CAH genotype in the family members with cryptic 21-hydroxylase deficiency is 21-OHCAH/21-OHCRYPTIC. Lod score analysis for linkage between the cryptogenic 21-OH trait and HLA gave a combined Lod score for males and females of theta = 0.00 of 3.409. Close genetic linkage between HLA and 21-OHCRYPTIC was thus established. This study provides support for the previously reported heterogeneity of 21-hydroxylase deficiency which may result from allelic variability at the locus for steroid 21-hydroxylase.
D006907:17-alpha-Hydroxypregnenolone / Q000097:blood; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000378:metabolism; D000735:Androstenedione / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003687:Dehydroepiandrosterone / Q000097:blood; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000172:deficiency*; D013739:Testosterone / Q000097:blood
D006680:HLA Antigens; D006908:Hydroxyprogesterones; D006907:17-alpha-Hydroxypregnenolone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase