一名因甲状腺球蛋白基因缺陷导致甲状腺肿大的临床甲状腺功能正常儿童：临床特征及遗传学研究
A clinically euthyroid child with a large goiter due to a thyroglobulin gene defect: clinical features and genetic studies.
作者信息
Hermanns Pia, Refetoff Samuel, Sriphrapradang Chutintorn, Pohlenz Joachim, Okamato Jessica, Slyper Leeyat, Slyper Arnold H
机构信息
Johannes Gutenberg Children's Hospital, Mainz, Germany.
出版信息
J Pediatr Endocrinol Metab. 2013;26(1-2):119-23. doi: 10.1515/jpem-2012-0287.
Abstract
A 10-year old child born to consanguineous parents presented with an extremely large goiter, a low free T4 level and free T4 index, and normal TSH concentration. The findings of undetectable thyroglobulin (TG) and low free T4, and an elevated free T3/free T4 ratio suggested the possibility of a defect in TG synthesis. Noteworthy aspects of this case were the extremely elevated thyroidal radioiodide uptake despite a normal TSH concentration and the fact that the reduction in the size of her goiter only occurred when her TSH was suppressed below the normal range. Gene sequencing revealed that the patient was homozygous for a donor splice site mutation in intron 30 (IVS30+1G>C). Isolation of RNA obtained from the thyroid gland by fine needle aspiration and sequencing of the TG cDNA confirmed the prediction that exon 30 was skipped, resulting in an in-frame loss of 46 amino acids.
摘要
一名近亲结婚父母所生的10岁儿童，出现了极大的甲状腺肿、低游离T4水平和游离T4指数，以及正常的促甲状腺激素（TSH）浓度。甲状腺球蛋白（TG）检测不到、游离T4降低以及游离T3/游离T4比值升高的结果提示了TG合成存在缺陷的可能性。该病例值得注意的方面是，尽管TSH浓度正常，但甲状腺放射性碘摄取极度升高，并且只有当她的TSH被抑制到正常范围以下时，甲状腺肿的大小才会缩小。基因测序显示，患者在第30内含子（IVS30+1G>C）的供体剪接位点突变上是纯合子。通过细针穿刺从甲状腺获取RNA并对TG cDNA进行测序，证实了外显子30被跳过的预测，导致46个氨基酸的框内缺失。
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