两个小说在巴西促性腺激素释放激素受体基因的突变患者hypogonadotropic性腺机能减退和正常的嗅觉。
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科斯塔EM Bedecarrats GY,这些IJ, Kaiser乌兰巴托、资助者、BB Latronico AC
两个小说在巴西促性腺激素释放激素受体基因的突变患者hypogonadotropic性腺机能减退和正常的嗅觉。
中国性金属底座。2001年6月,86 (6):2680 - 6。
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11397871 (在PubMed]
- 文摘
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几个激性腺素释放素受体基因的点突变中描述的一种常染色体隐性形式先天性孤立hypogonadotropic性腺机能减退(HH)。我们调查了17个巴西患者男性和7女性(10)来自14个不同的家庭,HH和正常的嗅觉。HH的诊断是基于缺失或不完整的性发育经过17年的年龄与低或正常的两性的LH水平和低水平的睾丸激素雌二醇的男性和女性。所有病人提供正常的嗅觉在嗅觉特定测试。促性腺激素受体基因的编码区放大了PCR直接测序。小说错义突变,Arg(139),位于守恒DRS主题第三跨膜交界处,第二个激性腺素释放素受体被细胞内循环的纯合状态与完整的HH一女。Arg(139)他的突变完全消除检测GnRH-binding活动和阻止GnRH-induced磷酸肌醇积累体外的刺激。在另一个家庭,一个新的复合杂合的突变(Asn(10)赖氨酸和Gln Arg(106))被确认在四兄弟姐妹(两名男性和两名女性)和部分HH。Gln(106)参数突变,位于第一个细胞外循环,先前描述,和体外分析表明,突变体受体能够结合促,但减少了亲和力。Asn(10)赖氨酸突变的细胞外伴域受体激性腺素释放素在体外也减少了亲和力。 In this family we also identified a previously described silent polymorphism at amino acid residue 151 in the second intracellular loop that segregated with the two inactivating mutations of the GnRH receptor. This polymorphism was also found in two unrelated patients with sporadic HH without GnRH receptor loss of function mutations. No mutations were identified in the remaining cases. A good correlation between genotype and phenotype was found in our patients. The woman, who is homozygous for the completely inactivating Arg(139)His mutation, has complete HH with undetectable serum basal LH and FSH levels that failed to respond to GnRH stimulation. In addition, the affected patients who are compound heterozygotes for the Asn(10)Lys/Gln(106)Arg mutations, have partial HH with low serum basal LH levels that were responsive to GnRH stimulation. No clinical or hormonal differences were found between HH patients with and without mutations in the GnRH receptor gene, indicating that these data do not contribute to the identification of HH patients with GnRH receptor mutations. In conclusion, we report the first naturally occurring mutation within the conserved DRS motif of the GnRH receptor in a female with complete HH and a novel compound heterozygous mutation (Asn(10)Lys and Gln(106)Arg) in a family with partial HH, increasing the repertoire of the inactivating mutations of the GnRH receptor.