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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098846/ https://www.ncbi.nlm.nih.gov/pubmed/30154845 http://dx.doi.org/10.1155/2018/8986475 |
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author | Chen, Xi Kong, Xiaohong Zhu, Jie Zhang, Tingting Li, Yanwei Ding, Guifeng Wang, Huijuan |
author_facet | Chen, Xi Kong, Xiaohong Zhu, Jie Zhang, Tingting Li, Yanwei Ding, Guifeng Wang, Huijuan |
author_sort | Chen, Xi |
collection | PubMed |
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 | Online Article Text |
id | pubmed-6098846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-60988462018-08-28 Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis Chen, Xi Kong, Xiaohong Zhu, Jie Zhang, Tingting Li, Yanwei Ding, Guifeng Wang, Huijuan Int J Endocrinol Research Article 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. Hindawi 2018-08-02 /pmc/articles/PMC6098846/ /pubmed/30154845 http://dx.doi.org/10.1155/2018/8986475 Text en Copyright © 2018 Xi Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Chen, Xi Kong, Xiaohong Zhu, Jie Zhang, Tingting Li, Yanwei Ding, Guifeng Wang, Huijuan Mutational Spectrum Analysis of Seven Genes Associated with Thyroid Dyshormonogenesis |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098846/ https://www.ncbi.nlm.nih.gov/pubmed/30154845 http://dx.doi.org/10.1155/2018/8986475 |
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