3例部分雄激素不敏感综合征男性雄激素受体基因中检测到点突变。
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桑德斯PT, Padayachi T, Tincello DG, Shalet SM, Wu FC
3例部分雄激素不敏感综合征男性雄激素受体基因中检测到点突变。
临床内分泌素(Oxf)。1992年9月,37(3):214 - 20。
- PubMed ID
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1424203 (查看PubMed］
- 摘要
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目的:测定雄激素反应性受损男性雄激素受体基因的序列，以确定其男性化不足的分子基础。设计:血液样本作为基因组DNA的来源。雄激素受体基因的部分被聚合酶链反应扩增并测序。患者:样本来自3名患者和5名正常生育对照组。患者均为46 XY，阳痿，外生殖器模糊，乳房发育不良，不孕症。测量:从外周血白细胞中纯化总细胞DNA。对寡核苷酸引物设计侧翼雄激素受体基因的个别外显子合成。通过聚合酶链式反应从细胞DNA样本中扩增雄激素受体的特定区域。扩增的DNA被纯化，测序并与发表的序列进行比较。结果:在所有三例患者中均检测到雄激素受体基因的点突变，但在正常对照样本中未检测到缺陷。 In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the DNA binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect. CONCLUSION: Patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methionine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein.