open access

Vol 71, No 2 (2020)
Original Paper
Published online: 2020-02-25
Submitted: 2019-10-20
Accepted: 2020-01-06
Get Citation

Genetic testing of PAX8 mutations associated with thyroid dysgenesis in Chinese congenital hypothyroidism patients

Miaomiao Li, Fang Wang, Xiuli Wang, Yucui Zang, Wenmiao Liu, Fengqi Wang, Lu Zhang, Qian Tang, Shiguo Liu, Dehua Zhao
DOI: 10.5603/EP.a2020.0004
·
Pubmed: 32096550
·
Endokrynologia Polska 2020;71(2):153-159.

open access

Vol 71, No 2 (2020)
Original Paper
Published online: 2020-02-25
Submitted: 2019-10-20
Accepted: 2020-01-06

Abstract

Introduction: Thyroid dysgenesis (TD) is the main cause of congenital hypothyroidism (CH), affecting nearly 1 in 2000–3000 newborns worldwide, as the most common neonatal endocrine disorder. Paired box gene 8 (PAX8), expressed during all stages of thyroid follicular cell, plays a key role in thyroid morphogenesis by a complex regulatory network. In conclusion, the genetic mechanism of PAX8 mutant in TD is still ambiguous; therefore, further research is needed.

Material and methods: Blood samples were collected from 289 TD patients in Shandong Province, China. Genomic DNA was extracted from peripheral blood. All the exons of PAX8 along with their exon-intro boundaries were amplified by PCR and analysed by Sanger sequencing.

Results: We identified three novel PAX8 nonsense mutations in three patients by sequence analysis of PAX8: Patient 1 (c.285C>G, p.Tyr95Ter), Patient 2 (c.747T>G, p.Tyr249Ter), and Patient 3 (c.786C>A, p.Tyr262Ter). All the three patients carrying PAX8 variants had obvious clinical phenotypes of thyroid anomaly, such as hypoplasia and athyreosis.

Conclusion: We conducted the largest worldwide PAX8 mutation screening so far in TD patients. Three presumably pathogenic PAX8 mutations were detected in 289 TD cases for the first time, showing the mutation rate of PAX8 is 1.04% in Chinese TD patients. In addition, our study expands the gene mutation spectrum of TD.

Abstract

Introduction: Thyroid dysgenesis (TD) is the main cause of congenital hypothyroidism (CH), affecting nearly 1 in 2000–3000 newborns worldwide, as the most common neonatal endocrine disorder. Paired box gene 8 (PAX8), expressed during all stages of thyroid follicular cell, plays a key role in thyroid morphogenesis by a complex regulatory network. In conclusion, the genetic mechanism of PAX8 mutant in TD is still ambiguous; therefore, further research is needed.

Material and methods: Blood samples were collected from 289 TD patients in Shandong Province, China. Genomic DNA was extracted from peripheral blood. All the exons of PAX8 along with their exon-intro boundaries were amplified by PCR and analysed by Sanger sequencing.

Results: We identified three novel PAX8 nonsense mutations in three patients by sequence analysis of PAX8: Patient 1 (c.285C>G, p.Tyr95Ter), Patient 2 (c.747T>G, p.Tyr249Ter), and Patient 3 (c.786C>A, p.Tyr262Ter). All the three patients carrying PAX8 variants had obvious clinical phenotypes of thyroid anomaly, such as hypoplasia and athyreosis.

Conclusion: We conducted the largest worldwide PAX8 mutation screening so far in TD patients. Three presumably pathogenic PAX8 mutations were detected in 289 TD cases for the first time, showing the mutation rate of PAX8 is 1.04% in Chinese TD patients. In addition, our study expands the gene mutation spectrum of TD.

Get Citation

Keywords

thyroid dysgenesis; paired box gene 8; mutation; Sanger sequencing

About this article
Title

Genetic testing of PAX8 mutations associated with thyroid dysgenesis in Chinese congenital hypothyroidism patients

Journal

Endokrynologia Polska

Issue

Vol 71, No 2 (2020)

Pages

153-159

Published online

2020-02-25

DOI

10.5603/EP.a2020.0004

Pubmed

32096550

Bibliographic record

Endokrynologia Polska 2020;71(2):153-159.

Keywords

thyroid dysgenesis
paired box gene 8
mutation
Sanger sequencing

Authors

Miaomiao Li
Fang Wang
Xiuli Wang
Yucui Zang
Wenmiao Liu
Fengqi Wang
Lu Zhang
Qian Tang
Shiguo Liu
Dehua Zhao

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