Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2
Hypogonadotropic hypogonadism in an adult female with a heterozygous hypomorphic mutation of SOX2
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DOI：
10.1530/eje-06-0606
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发表时间：
2007-02-01
影响因子：
5.8
通讯作者：
Ogata, Tsutomu
中科院分区：
文献类型：
--
作者：
Sato, Naoko;Kamachi, Yusuke;Ogata, Tsutomu
目的：杂合子SOX 2突变最近已被报道，导致孤立的低促性腺激素性性腺功能减退症（HH），除了眼睛和大脑的异常。在这里，我们报告了另一个杂合子亚型SOX 2突变和孤立的HH。患者：患者是一个28岁的日本女性先天性右无眼症和青春期发育不良，谁被发现有HH的促性腺激素释放激素试验（峰值血清LH，2.3 mIU/ml，峰值血清FSH，2.9 mIU/ml）。方法：利用鸡δ-1-晶状体蛋白基因（DC 5）和小鼠巢蛋白基因（Nes 30）的核心增强子序列，对SOX 2进行突变分析，并对突变蛋白进行功能研究。突变体SOX 2蛋白有一个严重减少（约10%）的DNA结合亲和力和显着减少（20-30%）的反式激活潜力，没有显性负效应。结论：结果提供了进一步的支持SOX 2在调节促性腺激素生产的积极作用。
Objective: Heterozygous SOX2 mutations have recently been reported to cause isolated hypogonadotropic hypogonadism (HH), in addition to ocular and brain abnormalities. Here, we report a further case with a heterozygous hypomorphic SOX2 mutation and isolated HH.Patient: The patient was a 28-year-old Japanese female with congenital right anophthalmia and poor pubertal development, who was found to have HH by a gonadotropin-releasing hormone test (peak serum LH, 2.3 mIU/ml; peak serum FSH, 2.9 mIU/ml). Other pituitary hormones were normal.Methods: We performed mutation analysis of SOX2 and functional studies of mutant SOX2 protein using the core enhancer sequence of the chicken delta-1-crystallin gene (DC5) and that of the mouse nestin gene (Nes30).Results: A heterozygous missense mutation (224T > A, Leu75Gln) was identified in the DNA-binding domain. The mutant SOX2 protein had a severely reduced (approximately 10%) DNA-binding affinity and a markedly diminished (20-30%) transactivation potential with no dominant negative effect.Conclusions: The results provide further support for the positive role of SOX2 in the regulation of gonadotropin production.