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Clinical and molecular characteristics of congenital hypothyroidism with DUOX2 mutations


Biallelic or monoallelic mutations in DUOX2 have caused congenital hypothyroidism (CH) with variable phenotypes from asymptomatic to permanent CH. This study was aimed to clarify molecular feature and clinical spectrum in CH with DUOX2 mutations.


This study included 62 transient or permanent CH patients with normal-sized or enlarged eutopic thyroid. All coding exons of DUOX2 and their intronic flanking sequences were amplified by PCR, and directly sequenced. As for novel sequence variant of DUOX2, functional studies were performed by measuring H2O2 generation in vitro. Clinical presentation was retrospectively reviewed based on medical records.


Fifteen different DUOX2 variants including 11 novel variants (p.N43Y, p.A72S, p.P96L, p.G206V, p.V779M, p.A1123T, p.Y1229C, p.R1334W, p.C1411Y, p.I1417F, p.Q202RfsX93) were identified in 21 of 62 patients, indicating 33.9% of prevalence. Functional single nucleotide polymorphism (SNP), p.H678R, was more frequently found in CH patients than in healthy individuals (allele frequency: 12.9 % vs. 5.5 %, P=0.023). DUOX2 variants were observed 11 out of 28 transient CH patients and 10 out of 32 permanent CH patients (39.3 % vs 31.3 %, P=0.593). At reevaluation, thyroid stimulating hormone (TSH) levels were 7.4±1.9 mU/L and 27.4±21.2 mU/L in transient and permanent CH with DUOX2 variants, respectively. Five patients with biallelic variants had higher initial TSH level (116.1±79.2 vs 50.2±50.2, P=0.049), and 3 out of 5 were determined as transient CH. Functional analysis revealed partially impaired H2O2 generation in 15 different DUOX2 mutants.


This study showed that DUOX2 mutation is a common cause of CH with normal-sized or enlarged eutopic thyroid. Clinical spectrum of DUOX2 mutations was variable, emphasizing the importance of alternative mechanism to compensate the function of DUOX2 or modifying factors to regulate DUOX2 expression. Long-term follow up for CH patients with DUOX2 variants should be needed.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kim, YM., Jin, H.Y., Lee, B.H. et al. Clinical and molecular characteristics of congenital hypothyroidism with DUOX2 mutations. Int J Pediatr Endocrinol 2013 (Suppl 1), O54 (2013).

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  • Single Nucleotide Polymorphism
  • Variable Phenotype
  • Hypothyroidism
  • Thyroid Stimulate Hormone
  • Flank Sequence