中国循证儿科杂志 ›› 2021, Vol. 16 ›› Issue (3): 241-244.

• 论著 • 上一篇    下一篇

DUOXA2基因相关先天性甲状腺功能减退症伴甲状腺肿大 1例并文献复习

陆效笑1, 王来栓2a吴冰冰2b杨琳2c汪吉梅1   

  1. 1 复旦大学附属妇产科医院新生儿科上海,200011;2 复旦大学附属儿科医院上海,201102;a 新生儿科,b 出生缺陷重点实验室,c 内分泌遗传代谢科
  • 收稿日期:2020-10-26 修回日期:2021-03-11 出版日期:2021-06-25 发布日期:2021-06-25
  • 通讯作者: 汪吉梅

DUOXA2 gene related congenital hypothyroidism with goiter: one case report and literature review

LU Xiaoxiao1, WANG Laishuan2a, WU Bingbing2b, YANG Lin2c, WANG Jimei1   

  1. 1 Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China,2  Children's Hospital of Fudan University, Shanghai 201102, China; a Department of Neonatology, b Key Laboratory of Birth Defects, c Department of Pediatric Endocrinology and Inherited Metabolic Diseases
  • Received:2020-10-26 Revised:2021-03-11 Online:2021-06-25 Published:2021-06-25
  • Contact: WANG Jimei

摘要: 目的:报告1例DUOXA2基因相关先天性甲状腺功能减退症(CH)病例,总结其临床特征及基因变异的特点。 方法:对收治的1例CH患儿进行临床表型及基因型分析,并以“DUOXA2基因”为关键词在中国知网、万方、维普和中国生物医学文献数据库中检索;以“DUOXA2 gene”or “dual oxidase maturation factor 2”为关键词在PubMed和Web of Science数据库中检索,检索时间均为建库至2020年8月16日,总结DUOXA2基因相关CH的临床特征及遗传学特点。 结果:患儿女,25日龄,新生儿筛查提示TSH 224 mU·L-1,血清甲状腺功能提示TSH 100 mU·L-1,FT4 0 pmol·L-1,甲状腺B超示双侧甲状腺肿大。临床外显子测序分析提示DUOXA2基因c.738C>G(p.Y246X)及c.341G>C(p.G114A)两个杂合致病变异位点。予口服左甲状腺素钠片,随访至3岁8个月,患儿智力及体格发育正常。文献检索结果显示,国内外已报道的由DUOXA2基因突变所致CH病例40例,其中19例有随访情况的描述, DUOXA2基因双位点变异与单位点变异的患儿在新生儿筛查时的TSH水平、确诊时的血清TSH水平差异均有统计学意义(P分别为0.023和0.003);确诊时的血清FT4水平、甲状腺大小、停药及停药后重新治疗的比例、疾病转归均差异无统计学意义。 结论:DUOXA2基因突变所致的CH如果TSH水平明显增高可能为双位点突变。

关键词: 先天性甲状腺功能减退症, 甲状腺肿大, DUOXA2基因

Abstract: Objective: We amied to report a case of DUOXA2 gene related congenital hypothyroidism (CH) and to summarize its clinical features and characteristics of gene variants. Methods: The clinical phenotype and genotype of a girl with CH admitted to the Children's Hospital of Fudan University were analyzed. We searched "DUOXA2 gene" or "dual oxidase maturation factor 2" in CNKI, Wanfang database, VIP database, China Biomedical Literature database, PubMed and Web of Science database. All the databases were searched from the inception to Aug 16, 2020. Results: The girl at the age of 25 days showed TSH 224 mU·L-1 by newborn screening, TSH 100 mU·L-1 and FT4 0 pmol·L-1 by serum thyroid function, and bilateral goiter by thyroid ultrasound. Clinical exome sequencing analysis showed DUOXA2 gene c.738C>G (p.Y246X) and c.341G>C (p.G114A) heterozygous pathogenic variants. Followed-up to 3 years and 8 months old, her intelligence and growth were normal after taking levothyroxine sodium tablets. Forty cases of DUOXA2 gene disease have been reported at home and abroad, of which 19 cases have follow-up data. The biallelic and monoallelic DUOXA2 variants have statistical significance in the TSH level at newborn screening and in the serum TSH level at diagnosis respectively (P1=0.023; P2=0.003), but serum FT4 level at diagnosis, thyroid size, withdrawal or retreatment after withdrawal and outcome were not statistically significant. Conclusion: It may be bialletic variants if the TSH level is significantly increased in DUOXA2 gene related CH.

Key words: congenital hypothyroidism, Goiter, DUOXA2