Mutation screening of DUOX2 in Chinese patients with congenital hypothyroidism

Background Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder in infancy. Dual oxidase 2 gene (DUOX2) mutations have been reported to be one of the leading genetic causes of CH. Aim The aim of this study was to screen for DUOX2 gene mutations among CH patients in the Guangxi Zhuang Autonomous Region of China and to define the relationships between DUOX2 genotypes and clinical phenotypes. Materials and methods Blood samples were collected from 45 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the DUOX2 gene together with their exon-intron boundaries were screened by Sanger sequencing. Results Sequencing analysis of DUOX2 in 45 CH patients revealed ten different variants in thirteen individuals. The variants included five known mutations, namely c.3329G > A (p.R1110Q), c.1588A > T (p.K530X), c.2635G > A (p.E879K), c.2524C > T (p.R842X) and c.4027G > T (p.L1343F), and one novel frame shift variant c.3340delC (p.L1114SfsX56), as well as four novel missense variants c.903G > T (p.W301C), c.2048G > T (p.R683L), c.1736T > C (p.L579P) and c.3413C > A (p.A1138D). The variant p.K530X is highly recurrent in our patient cohort but the clinical phenotypes vary greatly among those carrying this variant. Most patients with monoallelic or biallelic DUOX2 pathogenic variants turned out to be cases of transient congenital hypothyroidism (TCH), while three patients with triallelic DUOX2 pathogenic variants were associated with permanent congenital hypothyroidism (PCH). Conclusions The prevalence of DUOX2 pathogenic variants was high (29 %) among patients with CH in Guangxi, China. Monoallelic and biallelic DUOX2 pathogenic variants were mainly associated with TCH, while triallelic DUOX2 pathogenic variants were associated with PCH. Our study expanded the DUOX2 mutation spectrum, and functional studies of the novel mutations need to be conducted in the future.