The Prevalence, Clinical, and Molecular Characteristics of Congenital Hypothyroidism Caused by DUOX2 Mutations: A Population-Based Cohort Study in Guangzhou

Thyroid dyshormonogenesis (DH) has recently been reported to be more frequently associated with mutations in the dual oxidase 2 (DUOX2) gene. The present study was aimed to investigate the prevalence, clinical, and molecular characteristics of congenital hypothyroidism (CH) caused by DUOX2 mutations in Guangzhou. A population-based cohort of 156 patients with CH was recruited based on neonatal screening among 433 578 newborns born in Guangzhou from 2011 to 2012. Genetic analysis of DUOX2 was performed in 96 patients with suspected thyroid dyshormonogenesis (SDH) by PCR-amplified direct sequencing. Apart from 2 cases without ultrasonographic data, 118 (76.6%) of the 156 patients were classified as SDH and 36 (23.4%) as thyroid dysgenesis (TD) according to thyroid ultrasound at diagnosis. Genetic analysis revealed 23 different variants in 60 unrelated individuals (60/96, 62.5%), including 13 novel variants that were absent from HGMD, dbSNP databases, and the 50 normal controls. The novel missense variants were predicted to be pathogenic by SIFT and PolyPhen-2. The p.K530X was the most common mutation. Ninety-three percent of mutant alleles occurred in exons 5, 6, 9, 14, 17, 20, 25, 27, and 28. There were no significant differences in phenotypes between biallelic and monoallelic variants cases or between with-DUOX2 and non-DUOX2 variants cases. Most patients with DUOX2 defects (78.2%) were transient CH. In conclusion, the prevalence of DUOX2 pathogenic variants was high (62.5%) in this cohort. Thirteen novel probably pathologic variants were reported. The p.K530X was the most common mutation in the Chinese population. There was no correlation between DUOX2 genotypes and clinical phenotypes.