Duprez L, Parma J, Van Sande J, Rodien P, Sabine C, Abramowicz M, Dumont J E, Vassart G
Institut de Recherche Interdisciplinaire, Faculty of Medicine, University of Brussels, Belgium.
J Pediatr Endocrinol Metab. 1999 Apr;12 Suppl 1:295-302.
Gain of function and loss of function mutations of the TSH receptor have been implicated in the pathogenesis of various thyroid diseases. Gain of function mutations, when somatic, are the first cause of autonomous nodules; when germline, they are responsible for hereditary non-autoimmune toxic thyroid hyperplasia and for some cases of sporadic congenital hyperthyroidism. A subset of mutations modifying the receptor selectivity have recently been found to be involved in the pathogenesis of familial gestational hyperthyroidism. These mutations are of great interest for understanding the mechanism of receptor activation. Loss of function mutations of the TSH receptor are responsible for different phenotypes ranging from asymptomatic resistance to TSH to overt congenital hypothyroidism.
促甲状腺激素（TSH）受体的功能获得性和功能丧失性突变与多种甲状腺疾病的发病机制有关。功能获得性突变若为体细胞突变，是自主性结节的首要病因；若为种系突变，则导致遗传性非自身免疫性毒性甲状腺增生以及某些散发性先天性甲状腺功能亢进症病例。最近发现，一部分改变受体选择性的突变与家族性妊娠期甲状腺功能亢进症的发病机制有关。这些突变对于理解受体激活机制具有重要意义。TSH受体的功能丧失性突变导致从无症状性TSH抵抗到明显先天性甲状腺功能减退症等不同表型。
