促甲状腺素受体基因突变一个家系研究

目的：探讨1个甲状腺发育不良先天性甲状腺功能减退症(先天性甲减)患者家系促甲状腺素受体(TSHR)基因突变遗传规律。方法：调查包括先证者3代家系成员共计13人，检测血清甲状腺激素。用TKM法提取基因组DNA，PCR扩增TSHR基因第10外显子序列，对PCR产物正反向测序，测序结果同Genbank人TSHR基因序列对比。结果：先证者TSHR基因同时存在2个位点纯合子型点突变R450H／D727E，家系12人甲状腺功能均正常，6人为R450H／D727E杂合子型点突变，其中5人血清sTSH轻度升高。结论：R450H／D727E纯合子导致先证者甲状腺发育不良及先天性甲减，R450H／D727E杂合子甲状腺功能正常仅sTSH轻度升高。

Study on the Pedigree with Thyrotropin Receptor Gene Mutation

Objective: To illuminate the hereditary rule of the thyrotropin receptor (TSHR) gene mutation in patients with congenital hypothyroidism (CH) and the family. Methods: Thyroid hormone was detected in total 13 persons including the proband and his 12 relatives. Genome DNA was extracted by TKM method. Exon 10 of TSHR gene sequence was amplified, PCR production was detected by direct and reverse sequencing, and the results and human TSHR gene sequence Genbank were compared. Results: Two homozygous mutations of R 450 H/D 727E were found in the proband, the thyroid functions were normal in the 12 relatives. Two heterozygous mutations of R 450 H/D 727E were found in 6 relatives, among them serum sTSH level slightly elevated in 5 persons. Conclusions: Homozygous R 450 H/D 727E mutation led to CH in the proband. Heterozygous R 450 H/D 727E had normal thy roid function except a slightly elevation of sTSH.