A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene
A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene
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DOI：
10.1086/380999
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发表时间：
2004-01-01
影响因子：
9.8
通讯作者：
Refetoff, S
中科院分区：
文献类型：
--
作者：
Dumitrescu, AM;Liao, XH;Refetoff, S
甲状腺激素是碘甲状腺原氨酸，控制生长和发育，以及大脑功能和代谢。虽然甲状腺激素缺乏症可由激素合成和作用缺陷引起，但它与细胞激素转运缺陷无关。事实上，几类膜转运蛋白的生理作用仍然未知。我们现在报告，第一次，突变的单羧酸转运蛋白8（MCT8）基因，位于X染色体上，编码一个613个氨基酸的蛋白质与12个预测的跨膜结构域。两个不相关家族的先证者是具有异常的三种循环碘甲腺原氨酸相对浓度以及神经系统异常的男性，包括全面发育迟缓、中枢性张力减退、痉挛性四肢瘫痪、张力障碍运动、旋转性眼球震颤以及受损的凝视和听力。杂合子女性有一个温和的甲状腺表型，没有神经缺陷。这些发现确立了MCT 8作为甲状腺激素转运蛋白的生理重要性。
Thyroid hormones are iodothyronines that control growth and development, as well as brain function and metabolism. Although thyroid hormone deficiency can be caused by defects of hormone synthesis and action, it has not been linked to a defect in cellular hormone transport. In fact, the physiological role of the several classes of membrane transporters remains unknown. We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613 - amino acid protein with 12 predicted transmembrane domains. The propositi of two unrelated families are males with abnormal relative concentrations of three circulating iodothyronines, as well as neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter.