An androgen receptor gene mutation (E653K) in a family with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency as well as in partial androgen insensitivity
An androgen receptor gene mutation (E653K) in a family with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency as well as in partial androgen insensitivity
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DOI：
10.1210/jc.87.6.2623
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发表时间：
2002-06-01
影响因子：
5.8
通讯作者：
Wedell, A
中科院分区：
文献类型：
--
作者：
Giwercman, YL;Nordenskjöld, A;Wedell, A
在两个无关的瑞典家族中发现了雄激素受体（AR）变异体（E653 K）。一个家庭有两个女孩患有先天性肾上腺皮质增生症（CAH）由于类固醇21-羟化酶缺乏症。这些女孩表现出与CYP 21基因型相关的轻度男性化，她们从父亲那里遗传了AR基因突变，而父亲没有表现出雄激素不敏感的症状。另一个家庭有一个男孩，部分雄激素不敏感，生殖器模糊，他从母亲那里遗传了AR基因突变。突变体受体表现出反式激活能力在相同的范围内作为正常受体在高浓度的配体（1和10 nM的双氢睾酮），但缺乏或减少反式激活在低水平（0.01和0.1 nM）。在另外250名瑞典男性中没有发现这种受体变异。在5个不相关的CAH女孩与I172 N突变的CYP 21和最小的男性化的AR基因测序没有发现任何额外的偏离正常参考序列。此外，在AR基因多态性CAG重复序列的长度之间没有差异CAH女孩与I172 N突变谁表现出最小和严重的男性化，我们没有发现任何证据的偏斜X-失活。我们的结论是AR基因突变或多态性不是影响CAH女孩高雄激素症状程度的常见因素，AR E653 K突变与正常生殖器发育相容，尽管它可能导致易感个体的生殖器畸形。
An androgen receptor (AR) variant (E653K) was found in two unrelated Swedish families. One family had two girls affected with congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. The girls, who showed mild virilization in relation to their CYP21 genotype, had inherited the AR gene mutation from their father, who showed no symptoms of androgen insensitivity. The other family had a boy with partial androgen insensitivity and ambiguous genitalia, and he had inherited the AR gene mutation from his mother. The mutant receptor showed a transactivating capacity in the same range as the normal receptor at high concentrations of ligand (1 and 10 nM dihydrotestosterone), but absent or reduced transactivation at low levels (0.01 and 0.1 nM). The receptor variant was not found among 250 additional unselected Swedish men. Sequencing of the AR gene in five unrelated CAH girls with the I172N mutation in CYP21 and minimal virilization did not reveal any additional deviations from the normal reference sequence. In addition, there was no difference in lengths of the polymorphic CAG repeat in the AR gene between CAH girls with the I172N mutation who showed minimal and severe virilization, and we found no evidence of skewed X-inactivation. We conclude that AR gene mutations or polymorphisms are not a common factor influencing the degree of hyperandrogenic symptoms displayed by CAH girls, and that the AR E653K mutation is compatible with normal genital development, although it can cause genital malformations in susceptible individuals.