A novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure
A novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure
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DOI：
10.1210/jc.87.3.1151
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发表时间：
2002-03-01
影响因子：
5.8
通讯作者：
Aittomäki, K
中科院分区：
文献类型：
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作者：
Doherty, E;Pakarinen, P;Aittomäki, K
已知FSH受体（FSHR）的失活突变会导致女性卵巢功能衰竭、闭经和不孕。在FSHR基因中发现的第一个突变是错义突变（566 C-->T，预测Ala 189 Val转换），发现于几个芬兰患者，由于卵巢功能衰竭而原发性闭经。只有五个额外的，部分或完全失活，突变的FSHR已被报道。在这里，我们报告了一个新的FSHR突变，1255 G-->A，在芬兰女性原发闭经。该患者是FSHR基因中两个突变的复合杂合子：566 C->T，芬兰创始人突变，和1255 G->A，一种以前未鉴定的突变。新的突变位于FSHR第二跨膜延伸的外显子10中，它预测了蛋白质结构中的Ala 419 Thr变化。在功能测试中，突变显示对配体结合能力和亲和力的影响极小，但它几乎完全消除了cAMP第二信使反应。在另外40名芬兰卵巢早衰患者中，没有发现这两种FSHR突变（566 C->T或1255 G->A）。根据这项研究和以前的研究，FSHR突变仍然是卵巢衰竭的罕见原因。
Inactivating mutations of the FSH receptor (FSHR) are known to cause ovarian failure with amenorrhea and infertility in women. The first mutation identified in the FSHR gene was a missense mutation (566C-->T, predicting Ala189Val transition) found in several Finnish patients with primary amenorrhea due to ovarian failure. Only five additional, partially or totally inactivating, mutations of the FSHR have been reported. Here, we report a novel FSHR mutation, 1255G-->A, in a Finnish female with primary amenorrhea. The patient was a compound heterozygote for two mutations in the FSHR gene: 566C-->T, the Finnish founder mutation, and 1255G-->A, a previously unidentified mutation. The new mutation is located in exon 10 in the second transmembrane stretch of the FSHR, and it predicts an Ala419Thr change in the protein structure. In functional testing, the mutation was shown to have minimal effect on ligand binding capacity and affinity, but it almost totally abolished the cAMP second messenger response. Neither of the two FSHR mutations (566C-->T or 1255G-->A) was identified in 40 other Finnish patients with premature ovarian failure. Based on this and previous studies, FSHR mutations remain a rare cause of ovarian failure.