先天性甲状腺功能减退症(CH)是新生儿常见的内分泌遗传疾病，根据临床转归，可分为永久性和暂时性甲减。DUOX2基因突变会引起甲状腺激素合成障碍，最终导致CH。既往的研究发现DUOX2突变的基因型和临床表型不完全一致，其遗传模式尚不明确；另外，脑发育完成后甲功正常的暂时性CH患者是否需要长期激素替代治疗也尚无定论。我们收集了72例CH患者，通过基因筛查，发现46例患者携带有DUOX2基因突变，其中DUOX2基因突变能够解释41.7%的CH。我们推测DUOX2基因突变导致的CH呈常染色体隐性遗传模式，并且在脑发育完成后甲功正常的暂时性CH患者仍需要长期激素替代治疗。基于这一假设，通过构建DUOX基因复合杂合突变的斑马鱼，研究基因型与表型的关系；开展人群研究，明确携带DUOX2基因突变的暂时性CH患者甲功正常后停药是否会影响长期的生长发育。最终，通过我们的研究将会对人口素质的提升产生积极的影响。

Congenital hypothyroidism (CH) is a common genetic endocrinological diseases in newborns. According to the clinical outcome, it can be divided into permanent and temporary hypothyroidism. Mutations in DUOX2 gene cause disorder of thyroid hormone synthesis, which ultimately leads to CH. Previous studies found that genotype and clinical phenotype was not completely consistent in DUOX2 mutations. So the model of inheritance is not clear. In addition, temporary CH patients had normal thyroid function after the brain development. Whether these patients need long-term hormone replacement was also inconclusive. We collected 72 CH patients. After genetic scanning, 46 patients were found to have DUOX2 gene mutations. DUOX2 gene mutation was able to explain 41.7% of CH. We hypothesized that CH caused by DUOX2 gene mutation was in an autosomal recessive model and that CH patients with normal thyroid function after brain development require long-term hormone replacement therapy. Based on this hypothesis, zebrafish with compound heterozygous mutations of DUOX gene was constructed to study the relationship between genotype and phenotype. Population study was also carried out to clarify whether discontinue of hormone replacement(temporary CH patients carrying DUOX2 gene mutations have normal thyroid function) will influence the long-term growth and development. In the end, our work will have positive impact on promotion of population quality.