THRβ基因c.728G>A突变致甲状腺激素抵抗综合征家系6年随访

A 6-year follow-up of the family with resistance to thyroid hormone syndrome carrying the THRβgene c.728G>A mutation

目的:探索一个甲状腺激素抵抗综合征(RTH)家系致病基因突变及临床表型,并进行6年随访。方法:先证者及其5名家系成员纳入本研究。采集受试者外周静脉血,提取基因组DNA。PCR扩增THRβ基因,纯化PCR产物直接送至测序。定期随访RTH患者。结果:5名家系成员中,先证者父亲甲状腺功能符合RTH临床诊断。先证者及其父亲无甲亢甲减、甲状腺肿等临床表现。先证者父亲甲状腺彩超显示甲状腺左叶低回声结节。先证者及其父亲均携带THRβ基因第7外显子c.728G>A(p.Arg243Gln,p.R243Q)杂合突变。6年随访期间,先证者及其父亲无甲亢或甲减相关表现,未予药物治疗。先证者父亲甲状腺结节无明显增大,无其他恶性征象。结论:THRβ基因c.728G>A杂合突变是先证者及其父亲发病的遗传学病因,RTH需长期随访。

Objective:To detect clinical features and gene mutation in the family with resistance to thyroid hormone syndrome(RTH)and to conduct a six-year follow-up.Methods:The proband and her five family members were enrolled in this study for thyroid function,thyroid ultrasound and ECT examination.The THRβgene was considered for mutation screening.Genomic DNA was extracted from peripheral blood leukocytes.Direct sequencing was performed to screen for the mutation in the exon fragments in the proband and her family members.The proband and mutation carrier were followed up regularly.Results:Of the five family members,only her father showed elevated levels of thyroid hormone and TSH,which was consistent with RTH.Both the proband and her father had no signs of hypothyroidism,hyperthyroidism or goiter.However,the father showed a hypoechoic nodule in the left lobe without other malignant signs.Molecular analysis revealed a missense mutation c.728G>A(p.Arg243Gln,p.R243Q)in the exon 7 of THRβgene in two patients with RTH.During the six-year follow up,the proband and her father had no signs of hyperthyroidism or hypothyroidism and therefore were not treated with any drugs.The father showed no significant increase in thyroid nodule volume or any other malignant signs.Conclusion:The heterozyous mutation c.728G>A in the THRβgene was identified in the family with RTH,which requires long-term follow-up.