Krude H, Biebermann H, Göpel W, Grüters A
Department of Pediatrics, Humboldt University Berlin, Germany.
Exp Clin Endocrinol Diabetes. 1996;104 Suppl 4:117-20. doi: 10.1055/s-0029-1211717.
According to the central role of the TSH receptor for thyroid function and growth the gene for the TSH receptor is a possible candidate gene for mutations which result in an impairment of thyroid growth and function (Vassart and Dumont 1992). First evidence for the role of TSH receptor defects in the pathogenesis of congenital thyroid disorders was elucidated by the presence of activating germline mutations leading to congenital hyperthyroidism (Duprez et al., 1994). After the finding of partial loss-of-function mutations leading to hyperthyrotropinemia (Sunthornthepvarakul et al., 1995) it was speculated that a more severe phenotype with hypothyroidism and hypoplasia of the gland (thyroid dysgenesis) would be the result, if complete loss-of-function mutations like the isoleucine167 to asparagine mutation would occur in a homozygote or compound heterozygote state. The screening of TSHR gene mutations by SSCP in a well defined cohort of 100 children with congenital hypothyroidism (CH), diagnosed and followed since 1978 in the Childrens Hospital of Berlin, revealed one patient with hypoplasia of the thyroid to be positive for two compound heterozygote inactivating mutations of the TSHR gene, indicating thereby that the clinical approach to define phenotypes of interest could be helpful to understand the fundamental process of thyroid development.
鉴于促甲状腺激素（TSH）受体在甲状腺功能和生长中起核心作用，TSH受体基因可能是导致甲状腺生长和功能受损的突变的候选基因（瓦萨特和迪蒙，1992年）。先天性甲状腺疾病发病机制中TSH受体缺陷作用的首个证据是通过导致先天性甲状腺功能亢进的种系激活突变得以阐明（迪普雷兹等人，1994年）。在发现导致促甲状腺激素血症的部分功能丧失突变后（孙通泰普瓦拉库尔等人，1995年），有人推测，如果像异亮氨酸167突变为天冬酰胺这样的完全功能丧失突变以纯合子或复合杂合子状态出现，将会导致更严重的甲状腺功能减退和腺体发育不全（甲状腺发育异常）的表型。通过单链构象多态性（SSCP）对1978年以来在柏林儿童医院诊断并随访的100名先天性甲状腺功能减退症（CH）患儿的明确队列进行TSHR基因突变筛查，发现1例甲状腺发育不全患者的TSHR基因存在两个复合杂合子失活突变，这表明通过临床方法定义感兴趣的表型可能有助于理解甲状腺发育的基本过程。
