Prevalence, clinical manifestation, and molecular mechanism of congenital hypothyroidism due to DUOX2 abnormality

在日本，由双等位基因DUOX 2突变引起的先天性甲状腺功能减退症（CH）的患病率为1/44，000。在CH中，双等位基因DUOX 2突变的患病率为8/102（7.8%），双等位基因DUOX 2突变的遗传方式为常染色体隐性遗传。双等位基因DUOX 2突变所致的CH具有以下特征：永久性、短暂性或迟发性。新生儿期的临床表现是严重的，而他们在2岁时有所改善。环境因素如母体碘暴露可影响临床结果。生化研究并不总是显示碘组织的缺陷。与此相反，单等位基因DUOX 2突变很少（<1%）发生CH。与单等位基因DUOX 2突变相关的CH遗传方式是多因素的。3.7%的具有单等位基因DU 0X 2突变和单等位基因TSHR突变的受试者发展CH。我已经建立了体外测定来表征野生型或突变型DU 0X 2分子的功能。

The prevalence of congenital hypothyroidism (CH) due to biallelic DUOX2 mutations is 1/44,000 in Japan. In CH, the prevalence of biallelic DUOX2 mutations is 8/102 (7.8%).The inheritance mode of biallelic DUOX2 mutations is autosomal recessive. CH due to biallelic DUOX2 mutations has some characteristics as follows: It is permanent, transient, or late-onset. Clinical findings in neonatal period are severe, while they improve by the age of 2 years. Environmental factors such as maternal iodine exposure can affect clinical findings. Biochemical study does not always show defects of iodine organization. In contrast, monoallelic DUOX2 mutation rarely (<1%) develops CH. The inheritance mode of CH related to monoallelic DUOX2 mutation is multifactorial. 3.7 % of subjects having both monoallelic DUOX2 mutation and monoallelic TSHR mutation develop CH.I have established in vitro assay to characterize function of wild or mutant DUOX2 molecule.