Open Access

Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism

  • Authors:
    • Huijuan Wang
    • Xiaohong Kong
    • Yanrui Pei
    • Xuemei Cui
    • Yijie Zhu
    • Zixuan He
    • Yanxia Wang
    • Lirong Zhang
    • Lixia Zhuo
    • Chao Chen
    • Xiaoli Yan
  • View Affiliations

  • Published online on: April 16, 2020     https://doi.org/10.3892/mmr.2020.11078
  • Pages: 297-309
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder with a genetic origin. The purpose of the present study was to analyze the mutation spectrum of CH patients in China. A targeted next‑generation sequencing panel covering all exons of 29 CH‑related causative genes was used in 43 Han Chinese patients with CH [11 dysgenesis and 32 glands in situ (GIS)]. The functional impact and pathogenicity of detected variants were analyzed using a comprehensive bioinformatics approach and co‑segregation studies. A total of 47 rare non‑polymorphic variants in 9 target genes associated with thyroid hormone synthesis (DUOX2, DUOXA2, TPO, TG, SLC26A4 and SLC5A5), thyroid stimulating hormone resistance (TSHR) and central hypothyroidism (PROP1 and TRHR) were identified in 31 patients (31/43, 72%). Of these variants, 8 were novel, including 3 in DUOX2, 2 in TPO, 3 in TSHR and 1 in SLC5A5. Variants were mostly affected by DUOX2, TG, TPO and TSHR. Approximately 44% of the patients (19/43) carried DUOX2 variants. The mutation detection rates in patients with GIS were higher compared with patients with dysgenesis [25/32 (78%) vs. 6/11 (54%)]. Oligogenic mutations were detected in 25.6% of the total cases and 35% of the mutated cases. Genetic basis was ascertained in 13 patients, reaching a diagnosis detection rate of 30%. In conclusion, genetic defects in dyshormonogenesis, mainly in DUOX2, were the main genetic cause of CH in the Chinese population. Oligogenicity is highly involved in CH pathogenesis and may thus be an important factor in common phenotypic variability observed in patients with CH.
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July-2020
Volume 22 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang H, Kong X, Pei Y, Cui X, Zhu Y, He Z, Wang Y, Zhang L, Zhuo L, Chen C, Chen C, et al: Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism. Mol Med Rep 22: 297-309, 2020
APA
Wang, H., Kong, X., Pei, Y., Cui, X., Zhu, Y., He, Z. ... Yan, X. (2020). Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism. Molecular Medicine Reports, 22, 297-309. https://doi.org/10.3892/mmr.2020.11078
MLA
Wang, H., Kong, X., Pei, Y., Cui, X., Zhu, Y., He, Z., Wang, Y., Zhang, L., Zhuo, L., Chen, C., Yan, X."Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism". Molecular Medicine Reports 22.1 (2020): 297-309.
Chicago
Wang, H., Kong, X., Pei, Y., Cui, X., Zhu, Y., He, Z., Wang, Y., Zhang, L., Zhuo, L., Chen, C., Yan, X."Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism". Molecular Medicine Reports 22, no. 1 (2020): 297-309. https://doi.org/10.3892/mmr.2020.11078