Abstract
Background: Dual oxidase 2 (DUOX2) mutations are a cause of dyshormonogenesis (DH) and have been identified in patients with permanent congenital hypothyroidism (PH) and with transient hypothyroidism (TH). We aimed to elucidate the prevalence and phenotypical variations of DUOX2 mutations.
Methods: Forty-eight Japanese DH patients were enroled and analysed for sequence variants of DUOX2, DUOXA2, and TPO using polymerase chain reaction-amplified direct sequencing.
Results: Fourteen sequence variants of DUOX2, including 10 novel variants, were identified in 11 patients. DUOX2 variants were more prevalent (11/48, 22.9%) than TPO (3/48, 6.3%) (p=0.020). The prevalence of DUOX2 variants in TH was slightly, but not significantly, higher than in PH. Furthermore, one patient had digenic heterozygous sequence variants of both DUOX2 and TPO.
Conclusions: Our results suggest that DUOX2 mutations might be the most common cause of both PH and TH, and that phenotypes of these mutations might be milder than those of other causes.
Dedicated to: Professor Kenji Fujieda, who sadly passed away on March 19, 2010, during the completion of this work.
Acknowledgments:
We thank Risa Taniguchi and Kenta Takahashi for technical assistance. We also thank Dr. Kohei Sato (Department of Pediatrics, Sapporo Kosei General Hospital) and Dr. Wakako Jo (Department of Pediatrics, Hokkaido University Graduate School of Medicine) for collecting clinical information.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was partly supported by a Grant-in-Aid for Creative Bio-scientific Research from Asahikawa Medical College.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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