先天性甲状腺功能减退,甲状腺受损反应促甲状腺素(TSH)和循环甲状腺球蛋白缺席:新证据灭活TSH受体基因的突变。
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Tonacchera M, Agretti P, Pinchera Rosellini V, Perri, Collecchi P, Vitti P, Chiovato L
先天性甲状腺功能减退,甲状腺受损反应促甲状腺素(TSH)和循环甲状腺球蛋白缺席:新证据灭活TSH受体基因的突变。
中国性金属底座。2000年3月,85 (3):1001 - 8。
- PubMed ID
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10720030 (在PubMed]
- 文摘
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先天性甲状腺功能减退因受损甲状腺对TSH最初是由Stanbury描述。诊断为先天性甲状腺功能减退,甲状腺没TSH接受如果患者有先天性甲状腺功能减退,甲状腺的正常位置的脖子,甲状腺正常或萎缩性的大小,增加血清TSH水平,TSH的生物活性是完好无损,甲状腺对TSH刺激的反应却降低了。在所有最初描述病例血清甲状腺球蛋白是无法觉察的。我们描述一个22-yr-old女性病人严重甲状腺和智障。血清T4、T3含量低于方法的敏感性,与血清TSH水平升高。血清甲状腺球蛋白是无法觉察的。正常的发育不全的腺位于适当的颈部解剖位置在scintiscan被发现。牛TSH的腺体后没有回应政府的131我吸收,血清甲状腺激素和甲状腺球蛋白分泌。诊断为先天性甲状腺功能减退因TSH睡着被制定。遗传分析的先证者显示纯合灭活突变TSH受体没有先前描述。 The mutation consisted of the substitution of an isoleucine in place of a highly conserved threonine at position 477 in the first extracellular loop of the receptor (T477I). The brother, one sister of the father (whose DNA was not available), the mother of the propositus, one sister, and the brother were heterozygous for T477I. All the heterozygous persons were unaffected. After transfection in COS-7 cells, the mutant receptor displayed an extremely low expression at cell surface. At variance with cells transfected with the wild-type TSH receptor, cells transfected with the mutant T477I did not show constitutive activity for the adenylyl cyclase pathway. A dramatic reduction in the amount of cAMP accumulation after bovine TSH challenge was observed in cells transfected with the mutant T477I receptor. A structural defect in the mutant TSH receptor protein was probably responsible for the poor routing of the receptor to the cell membrane. This is the first time that a loss of function mutation of the TSH receptor is described in a patient with severe congenital hypothyroidism and absent circulating thyroglobulin due to TSH unresponsiveness and the first time that an inactivating mutation of the TSH receptor is described in the first extracellular loop.