The mutation screening in candidate genes related to thyroid dysgenesis by targeted next-generation sequencing panel in the Chinese congenital hypothyroidism
Rui-Jia Zhang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorGuang-lin Yang
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorFeng Cheng
Department of Laboratory Medicine, Fujian Children's Hospital, Fujian Provincial Maternity and Children's Hospital, Fuzhou, China
Search for more papers by this authorFeng Sun
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorYa Fang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorCao-Xu Zhang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorZheng Wang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorFeng-Yao Wu
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJun-Xiu Zhang
Department of Endocrinology, Maternal and Child Health Institute of Bozhou, Bozhou, China
Search for more papers by this authorShuang-Xia Zhao
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJun Liang
Department of Endocrinology, The Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Huai-Dong Song
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence Huai-Dong Song, The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Email: [email protected]
Search for more papers by this authorRui-Jia Zhang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorGuang-lin Yang
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorFeng Cheng
Department of Laboratory Medicine, Fujian Children's Hospital, Fujian Provincial Maternity and Children's Hospital, Fuzhou, China
Search for more papers by this authorFeng Sun
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorYa Fang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorCao-Xu Zhang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorZheng Wang
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorFeng-Yao Wu
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJun-Xiu Zhang
Department of Endocrinology, Maternal and Child Health Institute of Bozhou, Bozhou, China
Search for more papers by this authorShuang-Xia Zhao
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJun Liang
Department of Endocrinology, The Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Huai-Dong Song
The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence Huai-Dong Song, The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Email: [email protected]
Search for more papers by this authorRui-Jia Zhang, Guang-lin Yang, and Feng Cheng are joint first authors.
Jun Liang and Huai-Dong Song are joint co-corresponding authors.
Abstract
Objective
Congenital hypothyroidism (CH) is known to be due to thyroid dyshormonogenesis (DH), which is mostly inherited in an autosomal recessive inheritance pattern or thyroid dysgenesis (TD), whose inheritance pattern is controversial and whose molecular etiology remains poorly understood.
Design and Methods
The variants in 37 candidate genes of CH, including 25 genes related to TD, were screened by targeted exon sequencing in 205 Chinese patients whose CH cannot be explained by biallelic variants in genes related to DH. The inheritance pattern of the genes was analyzed in family trios or quartets.
Results
Of the 205 patients, 83 patients carried at least one variant in 19 genes related to TD, and 59 of those 83 patients harbored more than two variants in distinct candidate genes for CH. Biallelic or de novo variants in the genes related to TD in Chinese patients are rare. We also found nine probands carried only one heterozygous variant in the genes related to TD that were inherited from a euthyroid either paternal or maternal parent. These findings did not support the monogenic inheritance pattern of the genes related to TD in CH patients. Notably, in family trio or quartet analysis, of 36 patients carrying more than two variants in distinct genes, 24 patients carried these variants inherited from both their parents, which indicated that the oligogenic inheritance pattern of the genes related to TD should be considered in CH.
Conclusions
Our study expanded the variant spectrum of the genes related to TD in Chinese CH patients. It is rare that CH in Chinese patients could be explained by monogenic germline variants in genes related to TD. The hypothesis of an oligogenic origin of the CH should be considered.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| cen14577-sup-0001-Supplement_Table_1.xlsx20.3 KB | Supporting information. |
| cen14577-sup-0002-Supplement_Table_2.xlsx23.1 KB | Supporting information. |
| cen14577-sup-0003-Supplement_Table_3.xlsx13.6 KB | Supporting information. |
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