Deladoëy Johnny, Vassart Gilbert, Van Vliet Guy
Endocrinology Service and Research Center, Department of Pediatrics, Sainte-Justine Hospital, University of Montreal, Montreal, Que., Canada.
Endocr Dev. 2007;10:29-42. doi: 10.1159/000106818.
Most research on the molecular mechanisms of thyroid dysgenesis over the past decade has focussed on the Mendelian mechanisms that may account for the few (5%) cases in which there is an affected relative. This chapter first reviews methodological issues in the imaging techniques used to classify thyroid dysgenesis into its various forms (ectopic thyroid, agenesis, orthotopic hypoplasia and hemiagenesis). It then reviews the evidence that non-Mendelian mechanisms must be involved in the vast majority of cases of this disease, for which the percentage of sporadic cases and of discordance between monozygotic twins exceeds 95%. Among the mechanisms reviewed are early somatic mutations and epigenetic changes in genes involved in thyroid development such as the thyroid transcription factors TTF-1, TTF-2 and PAX-8. The possible role of extrathyroid genes involved in the control of migration of the median thyroid bud during embryogenesis, such as adhesion molecules, and of vascular factors involved in the stabilization of the bilobed structure of the thyroid is also discussed.
在过去十年中，大多数关于甲状腺发育不全分子机制的研究都集中在孟德尔机制上，这些机制可能解释少数（5%）有患病亲属的病例。本章首先回顾了用于将甲状腺发育不全分类为各种形式（异位甲状腺、发育不全、原位发育不全和半侧发育不全）的成像技术中的方法学问题。然后回顾了证据，表明绝大多数这种疾病的病例必定涉及非孟德尔机制，其中散发病例的比例以及同卵双胞胎之间的不一致性超过95%。所回顾的机制包括甲状腺发育相关基因（如甲状腺转录因子TTF-1、TTF-2和PAX-8）的早期体细胞突变和表观遗传变化。还讨论了在胚胎发生过程中参与控制甲状腺中芽迁移的甲状腺外基因（如黏附分子）以及参与甲状腺双叶结构稳定的血管因子的可能作用。
