Lichti-Kaiser Kristin, ZeRuth Gary, Jetten Anton M
Cell Biology Section, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
J Endocrinol Diabetes Obes. 2014 Apr;2(2):1024.
Congenital hypothyroidism (CH) is the most frequent endocrine disorder in neonates. While several genetic mutations have been identified that result in developmental defects of the thyroid gland or thyroid hormone synthesis, genetic factors have yet to be identified in many CH patients along with the mechanisms underlying their pathophysiology. Mutations in the gene encoding the Krüppel-like transcription factor, GLI-similar 3 (GLIS3) have been associated with the development of a syndrome characterized by congenital hypothyroidism and neonatal diabetes and similar phenotypes were observed in mouse knockout models of . Patients with GLIS3-mediated CH exhibit diminished serum levels of thyroxine (T4) and triiodothyronine (T3) and elevated thyroid stimulating hormone (TSH) and thyroglobulin (TG). However, the inconsistent presentation of clinical features associated with this CH has made it difficult to ascertain a causative mechanism. Future elucidation of the biological functions of GLIS3 in the thyroid will be crucial to the discovery of new therapeutic opportunities for the treatment of CH.
先天性甲状腺功能减退症（CH）是新生儿中最常见的内分泌疾病。虽然已经鉴定出几种导致甲状腺发育缺陷或甲状腺激素合成的基因突变，但许多CH患者的遗传因素及其病理生理学机制尚未确定。编码Krüppel样转录因子GLI-相似3（GLIS3）的基因突变与一种以先天性甲状腺功能减退症和新生儿糖尿病为特征的综合征的发生有关，并且在小鼠基因敲除模型中也观察到了类似的表型。GLIS3介导的CH患者血清甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平降低，促甲状腺激素（TSH）和甲状腺球蛋白（TG）升高。然而，与这种CH相关的临床特征表现不一致，使得难以确定其致病机制。未来阐明GLIS3在甲状腺中的生物学功能对于发现治疗CH的新治疗机会至关重要。
