OMIA:002210-9823 : Hypothyroidism, congenital, DUOX2-related in Sus scrofa (pig)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
History: This single-locus disorder is one of 10 created by the use of ENU mutagenesis, i.e. mutagenesis of sperm via injection of N-ethyl-N-nitrosourea into young boars, as reported by Hai et al. (2017).
Mapping: Cao et al. (2019) mapped this disorder to a region on "chromosome 1 (118-160 Mb) . . . which included 374 annotated genes."
Molecular basis: Whole-exome sequencing of two homozygous-mutant pigs, followed by filtering and segregation analysis, enabled Cao et al. (2019) to identify the likely causal variant as "(c.1226 A>G) that resulted in a highly conserved amino acid substitution (D409G) . . . in the DUOX2 gene. This mutation, located within an exonic splicing enhancer motif, caused aberrant splicing of DUOX2 transcripts and resulted in lower H2O2 production, which might cause a severe defect in thyroid hormone production."
Have human generated variants been created, e.g. through genetic engineering and gene editing
Clinical features: Cao et al. (2019) reported that affected pigs had "congenital nude skin and thyroid deficiency".
Bama Xiang Zhu, China (Pig) (VBO_0012741).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|DUOX2||dual oxidase 2||Sus scrofa||1||NC_010443.5 (126620468..126641406)||DUOX2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1115||Bama Xiang Zhu, China (Pig)||Congenital hypothyroidosis||DUOX2||missense||Naturally occurring variant||Sscrofa11.1||1||g.126625620A>G||c.1226A>G||p.(D409G)||ENU mutagenesis was used to create these pigs, the mutation is located within an exonic splicing enhancer motif and causes aberrant splicing of DUOX2 transcripts (Cao et al., 2019)||2019||30651277|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2019||Cao, C., Zhang, Y., Jia, Q., Wang, X., Zheng, Q., Zhang, H., Song, R., Li, Y., Luo, A., Hong, Q., Qin, G., Yao, J., Zhang, N., Wang, Y., Wang, H., Zhou, Q., Zhao, J. :|
|An exonic splicing enhancer mutation in <i>DUOX2</i> causes aberrant alternative splicing and severe congenital hypothyroidism in Bama pigs. Dis Model Mech 12, 2019. Pubmed reference: 30651277. DOI: 10.1242/dmm.036616.|
|2017||Hai, T., Cao, C., Shang, H., Guo, W., Mu, Y., Yang, S., Zhang, Y., Zheng, Q., Zhang, T., Wang, X., Liu, Y., Kong, Q., Li, K., Wang, D., Qi, M., Hong, Q., Zhang, R., Wang, X., Jia, Q., Wang, X., Qin, G., Li, Y., Luo, A., Jin, W., Yao, J., Huang, J., Zhang, H., Li, M., Xie, X., Zheng, X., Guo, K., Wang, Q., Zhang, S., Li, L., Xie, F., Zhang, Y., Weng, X., Yin, Z., Hu, K., Cong, Y., Zheng, P., Zou, H., Xin, L., Xia, J., Ruan, J., Li, H., Zhao, W., Yuan, J., Liu, Z., Gu, W., Li, M., Wang, Y., Wang, H., Yang, S., Liu, Z., Wei, H., Zhao, J., Zhou, Q., Meng, A. :|
|Pilot study of large-scale production of mutant pigs by ENU mutagenesis. Elife 6:e26248, 2017. Pubmed reference: 28639938. DOI: 10.7554/eLife.26248.|
- Created by Frank Nicholas on 20 Sep 2019
- Changed by Frank Nicholas on 20 Sep 2019
- Changed by Frank Nicholas on 21 Sep 2019
- Changed by Imke Tammen2 on 23 Feb 2021