先天性甲状腺功能减退和明显athyreosis复合杂合性或补偿甲状腺功能减退可能hemizygosity灭活突变的TSH受体。
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贝茨公园SM, Clifton-Bligh RJ, P, Chatterjee VK
先天性甲状腺功能减退和明显athyreosis复合杂合性或补偿甲状腺功能减退可能hemizygosity灭活突变的TSH受体。
中国性(Oxf)。2004年2月;60 (2):220 - 7。
- PubMed ID
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14725684 (在PubMed]
- 文摘
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目的:我们希望确定TSH受体(TSHR)基因的突变与先天性甲状腺功能减退,没有出现在两个兄弟姐妹父母的血缘关系。设计:pituitary-thyroid轴和甲状腺形态研究兄弟姐妹和他们的父母的影响。在每个主题TSHR基因进行了分析。测量:基底甲状腺功能一起循环甲状腺球蛋白水平测量在每个主题。此外,韦刺激在每个父测试进行。所有家庭成员接受甲状腺超声。TSHR基因从基因组DNA放大使用聚合酶链反应和受体突变被序列分析鉴定。结果:两个兄弟被诊断出患有严重的先天性甲状腺功能减退(19 - 21总T4 nmol / l, 160 - 230亩/ l对新生儿TSH筛查)。尽管放射碘扫描显示没有示踪剂摄取和超声成像在两个人没能证明甲状腺组织,建议完成athyreosis,循环甲状腺球蛋白水平可以衡量的。甲状腺的父母不和谐的现状:父亲,基线甲状腺功能(FT4 13 pmol / l, TSH 4亩/ l),韦后的峰值TSH水平刺激(30亩/ l)是正常的,他表现出一个适当的循环上升甲状腺激素对TSH升高; in contrast, in the mother, baseline thyroid function was abnormal (FT4 10 pmol/l, TSH 15 mU/l), the TSH response to TRH was exaggerated (110 mU/l), with no subsequent rise in circulating thyroid hormones. An eutopic, slightly hypoplastic thyroid gland was visualized on ultrasonography in the mother and her thyroid antibody status was negative. Both children were compound heterozygotes for missense (alanine to threonine at codon 553, A553T) and premature stop (tryptophan at codon 546, W546X) mutations in the fourth transmembrane domain of the TSH receptor. The mother and father were heterozygous for W546X and A553T mutations, respectively. Each mutation is known to abolish the function or cellular surface expression of the TSH receptor. CONCLUSIONS: Inactivating mutations in the TSH receptor can be associated with severe TSH resistance presenting as congenital hypothyroidism with apparent athyreosis. Our observations also suggest that heterozygosity for an inactivating TSHR mutation may be associated with compensated hypothyroidism and thyroid hypoplasia.