Levine L S, Dupont B, Lorenzen F, Pang S, Pollack M, Oberfield S, Kohn B, Lerner A, Cacciari E, Mantero F, Cassio A, Scaroni C, Chiumello G, Rondanini G F, Gargantini L, Giovannelli G, Virdis R, Bartolotta E, Migliori C, Pintor C, Tato L, Barboni F, New M I
J Clin Endocrinol Metab. 1980 Dec;51(6):1316-24. doi: 10.1210/jcem-51-6-1316.
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.
对124个因21-羟化酶缺乏所致先天性肾上腺皮质增生症（CAH）患者的家系进行了血清雄激素、17-羟孕酮浓度及HLA基因型测定。在8个家系中，我们发现16名青春期或青春期后的家庭成员，无论男女，有21-羟化酶缺乏的生化证据，但无雄激素过多、闭经或不孕的临床症状。我们将这些家庭成员定义为隐匿性21-羟化酶缺乏个体。在每一代中，隐匿性21-羟化酶缺乏的家庭成员HLA相同。有人提出这些家庭成员是遗传复合物，由于两个隐性基因缺陷导致21-羟化酶缺乏：1）在典型CAH（21-OHCAH）先证者中存在的严重21-羟化酶基因缺陷；2）轻度21-羟化酶基因缺陷（21-OHCRYPTIC）。因此，隐匿性21-羟化酶缺乏家庭成员的CAH基因型为21-OHCAH/21-OHCRYPTIC。对隐匿性21-OH性状与HLA之间的连锁进行Lod评分分析，男性和女性在θ = 0.00时的合并Lod评分为3.409。由此确立了HLA与21-OHCRYPTIC之间紧密的遗传连锁。本研究为先前报道的21-羟化酶缺乏的异质性提供了支持，这种异质性可能是由于类固醇21-羟化酶基因座的等位基因变异所致。
