Abstract：Objective To investigate the characteristics of DUOXA2 gene mutation and the genotype-phenotype relationship in children with congenital hypothyroidism (CH) in Guangzhou, China. Methods A total of 20 CH patients with suspected thyroid dyshormonogenesis who had no DUOX2 gene mutation were enrolled. These patients who were born between 2011 and 2012 were screened and diagnosed with CH in the Guangzhou Newborn Screening Center. PCR and direct sequencing were used to analyze DUOXA2 gene mutation. Results Among the 20 patients, 2 had p.Y246X/p.Y246X homozygous mutation; 4 had monoallelic heterozygous mutation, among whom 2 carried the known pathogenic mutation c.413-414insA, 1 carried p.Y246X, and 1 carried a novel mutation, p.G79R. Reevaluation was performed at the age of 2-3 years, and the results showed that the two patients with p.Y246X/p.Y246X homozygous mutation were manifested as transient and mild permanent CH, respectively. Among the four patients with monoallelic heterozygous mutation, the one who carried p.Y246X mutation was manifested as typical permanent CH, and the other three were manifested as transient CH. Conclusions DUOXA2 gene mutation is a common molecular pathogenic basis for CH children with suspected thyroid dyshormonogenesis in Guangzhou, and most of them are manifested as transient CH. There is no association between DUOXA2 genotypes and phenotypes. The novel mutation p.G79R is probably a pathogenic mutation.
TAN Min-Yi,HUANG Yong-Lan,LI Bei et al. Characteristics of DUOXA2 gene mutation in children with congenital hypothyroidism[J]. CJCP, 2017, 19(1): 59-63.
Tan M, Huang Y, Jiang X, et al. The Prevalence, clinical, and molecular characteristics of congenital hypothyroidism caused by DUOX2 mutations:A population-based cohort study in Guangzhou[J]. Horm Metab Res, 2016, 48(9):581-588.
[3]
Hashemipour M, Ghasemi M, Hovsepian S, et al. Etiology of congenital hypothyroidism in Isfahan:Does it different[J]. Adv Biomed Res, 2014, 3:21.
[4]
Albert BB, Cutfield WS, Webster D, et al. Etiology of increasing incidence of congenital hypothyroidism in New Zealand from 1993-2010[J]. J Clin Endocrinol Metab, 2012, 97(9):3155-3160.
[5]
Park KJ, Park HK, Kim YJ, et al. DUOX2 mutations are frequently associated with congenital hypothyroidism in the Korean population[J]. Ann Lab Med, 2016, 36(2):145-153.
[6]
Zamproni I, Grasberger H, Cortinovis F, et al. Biallelic inactivation of the dual oxidase maturation factor 2(DUOXA2) gene as a novel cause of congenital hypothyroidism[J]. J Clin Endocrinol Metab, 2008, 93(2):605-610.
Grasberger H, Refetoff S. Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent[J]. J Biol Chem, 2006, 281(27):18269-18272.
[9]
Liu S, Liu L, Niu X, et al. A novel missense mutation (I26M) in DUOXA2 causing congenital goiter hypothyroidism impairs NADPH oxidase activity but not protein expression[J]. J Clin Endocrinol Metab, 2015, 100(4):1225-1229.
[10]
Yi RH, Zhu WB, Yang LY, et al. A novel dual oxidase maturation factor 2 gene mutation for congenital hypothyroidism[J]. Int J Mol Med, 2013, 31(2):467-470.
