Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis
Objective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequen...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2018/8986475 |
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| author | Xi Chen Xiaohong Kong Jie Zhu Tingting Zhang Yanwei Li Guifeng Ding Huijuan Wang |
| author_facet | Xi Chen Xiaohong Kong Jie Zhu Tingting Zhang Yanwei Li Guifeng Ding Huijuan Wang |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | Objective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results. Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions. DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study. |
| format | Article |
| id | doaj-art-7581c05f86a44c2b85dc46bcd3c50a76 |
| institution | OA Journals |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
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| series | International Journal of Endocrinology |
| spelling | doaj-art-7581c05f86a44c2b85dc46bcd3c50a762025-08-20T02:06:57ZengWileyInternational Journal of Endocrinology1687-83371687-83452018-01-01201810.1155/2018/89864758986475Mutational Spectrum Analysis of Seven Genes Associated with Thyroid DyshormonogenesisXi Chen0Xiaohong Kong1Jie Zhu2Tingting Zhang3Yanwei Li4Guifeng Ding5Huijuan Wang6Center for Genetic & Metabolic Disorders, Maternal and Child Health Care Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaThe National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, ChinaThe National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, ChinaThe National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, ChinaThe National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, ChinaCenter for Genetic & Metabolic Disorders, Maternal and Child Health Care Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaThe National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, ChinaObjective. Thyroid dyshormonogenesis (DH) is a genetically heterogeneous inherited disorder caused by thyroid hormone synthesis abnormalities. This study aims at comprehensively characterizing the mutation spectrum in Chinese patients with DH. Subjects and Methods. We utilized next-generation sequencing to screen for mutations in seven DH-associated genes (TPO, DUOX2, TG, DUOXA2, SLC26A4, SLC5A5, and IYD) in 21 Chinese Han patients with DH from Xinjiang Province. Results. Twenty-eight rare nonpolymorphic variants were found in 19 patients (90.5%), including 19, 5, 3, and 1 variants in DUOX2, TG, DUOXA2, and SLC26A4, respectively. Thirteen (62%) patients carried monogenic mutations, and six (28.5%) carried oligogenic mutations. Fifteen (71%) patients carried 2 or more DUOX2 (14) or DUOXA2 (1) variants. The genetic basis of DH in nine (43%) patients harboring biallelic or triallelic pathogenic variants was resolved. Seventeen patients (81%) carried DUOX2 mutations, most commonly p.R1110Q or p.K530X. No correlations were found between DUOX2 mutation types or numbers and clinical phenotypes. Conclusions. DUOX2 mutations were the most predominant genetic alterations of DH in the study cohort. Oligogenicity may explain the genetic basis of disease in many DH patients. Functional studies and further clinical studies with larger DH patient cohorts are needed to validate the roles of the mutations identified in this study.http://dx.doi.org/10.1155/2018/8986475 |
| spellingShingle | Xi Chen Xiaohong Kong Jie Zhu Tingting Zhang Yanwei Li Guifeng Ding Huijuan Wang Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis International Journal of Endocrinology |
| title | Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
| title_full | Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
| title_fullStr | Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
| title_full_unstemmed | Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
| title_short | Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
| title_sort | mutational spectrum analysis of seven genes associated with thyroid dyshormonogenesis |
| url | http://dx.doi.org/10.1155/2018/8986475 |
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