TSH受体基因的种系突变nonautoimmune亚临床甲状腺功能减退的原因。
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阿尔贝蒂L, Proverbio MC, Costagliola年代,Romoli R, Boldrighini B, Vigone MC,韦伯G, Chiumello G, Beck-Peccoz P, Persani L
TSH受体基因的种系突变nonautoimmune亚临床甲状腺功能减退的原因。
中国性金属底座。2002年6月,87 (6):2549 - 55。
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12050212 (在PubMed]
- 文摘
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生殖系丧失突变的TSH受体(TSHR)基因已经有部分或完整的家庭中描述TSH阻力。大型TSH海拔一般纯合子或复合杂合的患者中发现的突变。在这项研究中,我们测序整个TSHR基因在一系列10无关的轻微的患者(6.6 - -14.9亩/升),中等(24-46亩/升)海拔的血清TSH,与绝对正常的自由甲状腺激素浓度有关。在所有患者中甲状腺体积是正常的,除了两个适度发育不全。自身免疫性甲状腺疾病的基础上被排除在所有的病人临床和生化参数。八个病人至少有一个一级相对轴承相同的生化的画面。TSHR基因突变检测10例中4例通过分析从边缘白细胞DNA。复合杂合性(P162A孕产妇等位基因,和小说突变C600R父亲)被发现在病人最高的TSH水平。只有一个TSHR基因突变在剩下的三个案例,也没有改变TSHR基因启动子被发现在所有这些渊源者。一种新的突变(L467P)检测到的等位基因在一个病人和她的同卵双胞胎。 Previously described inactive mutants, T655Delta and C41S, were detected in the other two cases. When tested on several occasions, circulating TSH values fluctuating above the upper limit of the normal range could be shown in heterozygous subjects of these families. A dominant mode of inheritance of the biochemical alterations was detected in these cases. Mutant TSHRs were studied during transient expression in COS7 and HEK293T cells. Their TSH-independent cAMP accumulation activities were very low or similar to mock-transfected cells, and no increases were seen after maximal hormone stimulation. Flow cytometry experiments showed a poor level of expression of all mutant TSHRs at the cell membrane. In conclusion, we found several loss-of-function mutations of TSHR, including two novel ones, in a series of unrelated patients with slightly elevated TSH levels. Therefore, partial resistance to TSH action is a frequent finding among patients with slight hyperthyrotropinemia of nonautoimmune origin. Germline mutations of TSHR may be associated with serum TSH values fluctuating above the upper limit of the normal range, also in the heterozygous state.