宁波地区先天性甲状腺功能减低症相关基因筛查情况分析

Analysis of congenital hypothyroidism-related genetic screening in Ningbo

目的 了解宁波市新生儿先天性甲状腺功能减低症基因筛查情况。方法 收集2021年宁波市出生的2060例活产新生儿的足跟血,进行生化筛查以及干血斑DNA提取,应用靶向高通量测序技术对候选致病基因(DUOX2、DUOXA2、TG、TSHR、TSHB、THRA、THRB、TPO、PAX8)进行联合筛查,并分析筛查结果。结果 2060例活产新生儿中发现98例新生儿为携带者,携带率约4.75%(98/2060),本研究中候选基因携带率由高到低分别为DUOX2基因3.93%(81/2060)、DUOXA2基因0.73%(15/2060)、TG基因0.05%(1/2060)以及TSHR基因0.05%(1/2060),未筛查出携带TSHB基因、THRA基因、THRB基因、TPO基因、PAX8基因的新生儿,考虑与样本量不足有关,其中有2例携带DUOX2基因的新生儿,根据其TSH值临床确诊为先天性甲状腺功能减低症。结论 宁波地区新生儿基因筛查联合促甲状腺素值可以了解先天性甲状腺功能减低症人群基因突变率、携带率,为宁波地区制定最佳筛查及确诊方案提供依据,目前发现的致病基因及其致病位点可为未来的基因治疗提供一定依据。

Objective To investigate the genetic screening of neonatal congenital hypothyroidism in Ningbo. Methods Heel blood of 2060 newborns in Ningbo in 2021 were collected for biochemical screening and DNA extraction from dried blood spots. Then, targeted high-throughput sequencing technology was applied to co-screen candidate pathogenic genes(DUOX2, DUOXA2, TG, TSHR, TSHB, THRA, THRB, TPO, PAX8) and the screening results were analyzed. Results 98 newborns were found to be carriers among 2060 live births, with a carrier rate of about 4.75%(98/2060). The candidate gene carrier rates from highest to lowest in this study were 3.93%(81/2060) for DUOX2 gene, 0.73%(15/2060) for DUOXA2 gene,0.05%(1/2060) for TG gene, and 0.05%(1/2060) for TSHR gene. In addition, this study did not screen out newborns with TSHB gene, THRA gene, THRB gene, TPO gene and PAX8 gene, which was considered to be related to insufficient sample size.2 newborns carrying DUOX2 gene were clinically diagnosed with congenital hypothyroidism based on their TSH values.Conclusion The genetic screening of newborns in Ningbo combined with thyroid stimulating hormone values can understand the mutation rate and carrier rate of congenital hypothyroidism population, and provide a basis for the best screening and diagnosis plan in Ningbo, the current discovery of disease-causing genes and their causative loci can provide a basis for future gene therapy.