MOLECULAR-GENETICS OF STEROID 5-ALPHA-REDUCTASE-2 DEFICIENCY
MOLECULAR-GENETICS OF STEROID 5-ALPHA-REDUCTASE-2 DEFICIENCY
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类固醇 5-α-还原酶-2缺乏症的分子遗传学研究
DOI：
10.1172/jci115954
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发表时间：
1992-09-01
影响因子：
15.9
通讯作者：
RUSSELL, DW
中科院分区：
文献类型：
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作者：
THIGPEN, AE;DAVIS, DL;RUSSELL, DW
类固醇5-α-还原酶的两个同工酶由不同的基因座编码，催化睾酮转化为双氢睾酮。2型同工酶的遗传缺陷导致男性假两性畸形，即受影响的男性具有正常的内部泌尿生殖道，但外部生殖器类似于女性。克隆了5-α-还原酶2型基因(基因符号SRD5A2)，该基因含有5个外显子和4个内含子。通过体细胞杂交定位和染色体原位杂交，将该基因定位于染色体2带p23。对SRD5A2基因进行分子分析，在23个5-α-还原酶缺乏症家系的11个纯合子、6个复合杂合子和4个推测的复合杂合子中发现了18个突变。在19个不同的种族背景中检测到6个明显的重复突变。在两名患者中，突变酶的催化效率与疾病的严重程度相关。复合杂合子的高比例表明，5-α-还原酶2型基因突变的携带者频率可能比之前认为的更高。
Two isozymes of steroid 5-alpha-reductase encoded by separate loci catalyze the conversion of testosterone to dihydrotestosterone. Inherited defects in the type 2 isozyme lead to male pseudohermaphroditism in which affected males have a normal internal urogenital tract but external genitalia resembling those of a female. The 5-alpha-reductase type 2 gene (gene symbol SRD5A2) was cloned and shown to contain five exons and four introns. The gene was localized to chromosome 2 band p23 by somatic cell hybrid mapping and chromosomal in situ hybridization. Molecular analysis of the SRD5A2 gene resulted in the identification of 18 mutations in 11 homozygotes, 6 compound heterozygotes, and 4 inferred compound heterozygotes from 23 families with 5-alpha-reductase deficiency. 6 apparent recurrent mutations were detected in 19 different ethnic backgrounds. In two patients, the catalytic efficiency of the mutant enzymes correlated with the severity of the disease. The high proportion of compound heterozygotes suggests that the carrier frequency of mutations in the 5-alpha-reductase type 2 gene may be higher than previously thought.