Abstract
Background: The objective of the study was to determine the genetic basis of goitrous congenital hypothyroidism (GCH) in Chinese siblings.
Methods: The proband and her younger brother with GCH were enrolled for molecular analysis of the dual oxidase 2 (DUOX2), dual oxidase maturation factor 2 (DUOXA2), and thyroid peroxidase (TPO) genes. Mutation screening was performed by Sanger sequencing the fragments amplified from genomic DNA. The detected mutations were verified among the close relatives of the patients and 105 controls. All participants underwent clinical examination and laboratory tests.
Results: Analysis of the TPO gene revealed two heterozygous mutations, the frameshift mutation c.2422delT in the exon14 of the TPO gene, that has been reported previously, and a novel missense mutation c.1682C>T (p.T561M) in the exon10 of the TPO gene. Nine family members of the patients were enrolled for mutation screening. The patients’ parents and grandfathers harbored a single heterozygous mutation. The germline mutations from this family were consistent with an autosomal recessive inheritance pattern. No mutations in the DUOXA2 and DUOX2 genes were observed.
Conclusions: The inactivating mutations (c.2422delT and p.T561M) in the TPO gene were identified in the Chinese siblings with GCH. The compound heterozygous mutations can cause GCH.
Acknowledgments
We thank the patients and their family members and the controls who agreed to participate in this study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. The authors have made the following declarations regarding their contributions: Shao-Gang Ma was the project leader for the primary work and wrote the manuscript. Xiao Zheng, Ya-Li Qiu, Man-Li Guo, and Xiao-Juan Shao searched databases and performed data analysis. All authors reviewed the manuscript and contributed to the preparation of the manuscript.
Research funding: This work was supported by the Social Development Project of Huai’an City (grant number: HAS2014005).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(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.
Trial registration: ChiCTR-CCS-14004734.
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