甲状腺球蛋白增高的先天性甲状腺功能减退症1例报告并文献复习

Congenital hypothyroidism with elevated thyroglobulin:a case report and literature review

目的探讨甲状腺球蛋白(TG)增高的先天性甲状腺功能减退症(CH)家系的临床特征及TG基因变异特征。方法回顾分析1个TG增高的CH家系的临床及TG基因检测结果,并复习相关国内外文献。结果先证者,女,45日龄,生后黄疸消褪延迟伴便秘。甲状腺功能检测提示为CH,同时发现TG水平增高。基因检测结果显示患儿TG基因存在c.2149 C>T和c.5401+113 A>G的复合杂合变异;Sanger测序验证c.2149 C>T来源于父亲,c.5401+113 A>G来源于母亲,其哥哥携带c.5401+113A>G杂合变异。患儿哥哥及父母表型正常。c.2149C>T及c.5401+113A>G变异尚未见文献报道,根据美国遗传变异分类标准与指南分别为疑似致病变异及临床意义未明变异。结论确诊TG基因变异引起CH患者TG水平增高,并发现2个新的TG基因变异位点。

Objective To investigate the clinical characteristics and TG gene variation characteristics of congenital hypothyroidism(CH)families with increased thyroglobulin(TG).Methods The clinical data and TG gene test results of a CH family with elevated TG were retrospectively analyzed and relevant domestic and foreign literature was reviewed.Results The proband,a 45-day-old girl,suffered from delayed resolution of jaundice and constipation.The thyroid function test indicated CH,and the level of TG was increased.The genetic results showed compound heterozygous mutations of c.2149 C>T and c.5401+113 A>G in the TG gene of the children.Sanger sequencing confirmed that c.2149 C>T was from father and c.5401+113 A>G was from mother,and a heterozygous mutation of c.5401+113 A>G was carried by his elder brother.The phenotypes of his elder brother and parents were normal.The mutations of c.2149 C>T and c.5401+113 A>G have not been reported in the literature,and these two variants were classified as likely pathogenic and unknown clinical significance according to the American genetic variation classification standards and guidelines.Conclusions It was confirmed that TG gene mutations caused an increase in TG levels in CH patients,and two new TG gene mutation sites were found.