Research Papers:

Genetic and functional analysis of two missense DUOX2 mutations in congenital hypothyroidism and goiter

Shiguo Liu, Wenhui Zhang, Liqin Zhang, Hui Zou, Kunna Lu, Qiang Li, Hongfei Xia, Shengli Yan _ and Xu Ma

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Oncotarget. 2018; 9:4366-4374. https://doi.org/10.18632/oncotarget.10525

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Shiguo Liu1,2,*, Wenhui Zhang3,4,*, Liqin Zhang5, Hui Zou6, Kunna Lu7, Qiang Li8, Hongfei Xia9,10,11, Shengli Yan3, Xu Ma9,10,11

1Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

2Genetic Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

3Endocrinology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

4Endocrinology Department, Liaocheng People’s Hospital, Liaocheng, 252002, China

5Neonatal Screening Center, Qingdao Women & Children Medical Healthcare Center, Qingdao, 266003, China

6Neonatal Screening Center, Jinan Women & Children Medical Healthcare Center, Jinan, 250000, China

7Endocrinology Department, The Affiliated Hospital of Taishan Medical College, Taian, 271000, China

8Andrology Department, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China

9Graduate School, Peking Union Medical College, Beijing, 100000, China

10National Research Institute for Family Planning, Beijing, 100081, China

11World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, 100000, China

*These authors have contributed equally to this work

Correspondence to:

Shengli Yan, email: [email protected]

Xu Ma, email: [email protected]

Keywords: congenital hypothyroidism, DUOX2, DUOXA2, mutation, function

Received: January 07, 2016     Accepted: May 20, 2016     Published: July 11, 2016


Mutations in the dual oxidase 2 gene (DUOX2) impair hydrogen peroxide (H2O2) production and cause dyshormonogenesis. In addition, these mutations have been implicated in autosomal recessive congenital hypothyroidism (CH) with goiter. In this study, we identified DUOX2 mutations that were causative for CH and explored the effects of these mutations on DUOX2 function. Blood samples were collected from 10 infants born with CH and goiter to unrelated parents. We extracted genomic DNA and sequenced all exons by polymerase chain reaction direct sequencing. The effects of DUOX2 mutations were characterized by H2O2 production assays and cycloheximide (CHX) chase experiments. Sequence analysis revealed one novel DUOX2 mutation and one known DUOX2 mutation in unrelated families: c.1060C>T (p.R354W) and c.3616 G>A (p.A1206T). Both mutations impaired H2O2 production. CHX chase experiments demonstrated the DUOX2 mutants had shorter half-lives and degraded more rapidly than wild-type DUOX2. Our study identified two novel DUOX2 mutations in Chinese patients with CH and goiter, which were responsible for the deficit in the organification process.

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