Yanase T, Kagimoto M, Matsui N, Simpson E R, Waterman M R
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235.
Mol Cell Endocrinol. 1988 Oct;59(3):249-53. doi: 10.1016/0303-7207(88)90110-4.
Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.
类固醇17α-羟化酶（细胞色素P-450(17)α）介导17α-羟化酶和17,20-裂解酶活性。17α-羟化酶缺乏症是一种相对罕见的疾病，其特征在于这些活性中的一种或两种存在缺陷。缺陷变异性的分子基础尚未完全了解。我们已经确定了一名患有17α-羟化酶/17,20-裂解酶联合缺乏症的日本患者的突变型P-450(17)α基因的外显子序列。在P-450(17)α基因外显子1的第17位氨基酸位置发现了由于单点突变导致的终止密码子（TGA）。该基因N端区域存在终止密码子导致肾上腺皮质和卵巢中缺乏功能性P-450(17)α蛋白，因此该患者出现高血压、原发性闭经和骨质疏松症。
