Objective: To explore the mutation characteristics of pathogenic genes in children with congenital hypothyroidism (CH) in Fujian. Methods: The clinical data of 116 unrelated CH children diagnosed in Fujian Provincial Maternal and Child Health Hospital from January 2019 to September 2020 were retrospectively analyzed, including 50 females and 66 males, with an average age of (20±10) days at diagnosis. Targeted exome sequencing technology was used to detect the mutation frequency, type and distribution characteristics of 29 genes related to thyroxine synthesis or thyroid development. Results: Three hundred and fifty-one potential functional mutations were detected in 105 of 116 CH patients, with a detection rate of 90.5% (105/116). DUOX2 (66.4%, 77/116) was the most frequent mutated gene, followed by TG (23.3%, 27/116), DUOXA1 (23.3%, 27/116), and TPO (12.1%, 14/116), which were all involved in thyroid hormone synthesis. Among the 105 children with CH, 70 cases carried double allele mutation. Except for 3 cases of thyroid dysplasia related genes (2 cases of TSHR and 1 case of GLIS3), the rest were also related to thyroid hormone synthesis. The gene with the highest carrier rate was DUOX2 (68.8%, 59/70), followed by TG (8.6%, 6/70), TPO (4.3%, 3/70), DUOXA2 (1.4%, 1/70) and DUOXA1 (1.4%, 1/70). Conclusion: The main mutated genes in CH children in Fujian are the key genes involved in thyroid hormone synthesis, such as DUOX2, TG and TPO.
目的： 探讨福建地区先天性甲状腺功能减退症（CH）患儿相关致病基因的突变特点。 方法： 回顾性分析2019年1月至2020年9月116例在福建省妇幼保健院临床确诊的无血缘关系的CH患儿的临床资料，其中女50例，男66例，确诊时平均年龄为（20±10）d。采用靶向外显子组测序技术检测患儿29个甲状腺素合成或甲状腺发育相关基因的突变频率、类型及分布特点。 结果： 在116例CH患儿中，105例共检出351个潜在致病基因突变，检出率为90.5%（105/116）；其中，突变频率最高的基因为DUOX2（66.4%，77/116），其次为TG（23.3%，27/116）、DUOXA1（23.3%，27/116）和TPO（12.1%，14/116），均与甲状腺激素合成有关。而这105例患儿中，70例携带双等位基因突变，除3例为甲状腺发育不良相关基因（2例TSHR和1例GLIS3）外，其余的也均与甲状腺激素合成有关，携带率最高的基因为DUOX2（68.8%，59/70），其次是TG（8.6%，6/70）、TPO（4.3%，3/70）、DUOXA2（1.4%，1/70）和DUOXA1（1.4%，1/70）。 结论： 福建地区CH患儿的主要突变基因是参与甲状腺激素合成过程中的关键基因，如DUOX2、TG和TPO。.