NONSENSE MUTATION CAUSING STEROID 21-HYDROXYLASE DEFICIENCY
NONSENSE MUTATION CAUSING STEROID 21-HYDROXYLASE DEFICIENCY
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DOI：
10.1172/jci113562
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发表时间：
1988-07-01
影响因子：
15.9
通讯作者：
WHITE, PC
中科院分区：
文献类型：
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作者：
GLOBERMAN, H;AMOR, M;WHITE, PC
我们确定了一个突变CYP21B基因的序列，该基因分离自一个由于类固醇21-羟化酶缺乏而导致的严重的“盐消耗”型先天性肾上腺增生的患者。该基因的密码子318由编码谷氨酰胺的CAG变为无义密码子TAG。据预测，由于翻译的过早终止，这将导致完全无功能的酶。此外，将克隆的突变基因转染到小鼠Y1肾上腺细胞中，与转染的正常CYP21B基因相比，产生的mRNA水平降低。通过特异性寡核苷酸探针杂交确定，20例21-羟化酶缺乏症患者中有3例携带该突变。这种突变在正常的CYP21A假基因中也可以看到，因此它在异常的CYP21B基因中的存在可能是基因转换事件的结果。
We determined the sequence of a mutant CYP21B gene isolated from a patient with the severe, "salt-wasting" form of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Codon 318 in this gene is changed from CAG, encoding glutamine, to TAG, a nonsense codon. This is predicted to result in a completely nonfunctional enzyme due to premature termination of translation. In addition, when the cloned mutant gene was transfected into mouse Y1 adrenal cells, the resulting mRNA levels were decreased compared with transfected normal CYP21B genes. This mutation was carried by 3 of 20 unrelated patients with 21-hydroxylase deficiency alleles as determined by hybridization with a specific oligonucleotide probe. This mutation is also seen in the normal CYP21A pseudogene, so that its presence in the abnormal CYP21B gene may be the result of a gene conversion event.