Utility of systematic <i>TSHR</i> gene testing in adults with hyperthyroidism lacking overt autoimmunity and diffuse uptake on thyroid scintigraphy

Patel, Kashyap; Knight, Bridget; Aziz, Aftab; Babiker, Tarig; Avades, Tamar; Findlay, Joanna; Cox, Sue; Dimitropoulos, Ioannis; Tysoe, Carolyn; Panicker, Vijay; Vaidya, Bijay

doi:10.1111/cen.13892

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…Among these genes, those that have received more attention include (1): the thyroid stimulating hormone receptor (TSHR) gene. TSHR gene mutations are one of the causes of non-autoimmune hyperthyroidism ( 6 , 7 ), and neonatal non-autoimmune hyperthyroidism is associated with the TSHR gene c.1856A>G (p.Asp619Gly) heterozygous mutation ( 8 ); (2) the cytotoxic T-lymphocyte associated protein 4 (CTLA4) gene. CTLA-4 gene mutations in the Chinese Han population are related to the development of hyperthyroidism ( 9 – 11 ); (3) the thyroid globulin (TG) gene.…”

Section: Introductionmentioning

confidence: 99%

Functional enrichment analysis of mutated genes in children with hyperthyroidism

Mao,

Tang,

et al. 2023

Front. Endocrinol.

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ObjectiveHyperthyroidism in Chinese children is relatively high and has been increasing in recent years, which has a significant impact on their healthy development. Hyperthyroidism is a polygenic disorder that presents greater challenges in terms of prediction and treatment than monogenic diseases. This study aims to elucidate the associated functions and gene sets of mutated genes in children with hyperthyroidism in terms of the gene ontology through GO enrichment analysis and in terms of biological signaling pathways through KEGG enrichment analysis, thereby enhancing our understanding of the expected effects of multiple mutated genes on hyperthyroidism in children.MethodsWhole-exome sequencing was performed on the DNA samples of children with hyperthyroidism. Screening for pathogenic genes related to hyperthyroidism in affected children was performed using the publicly available disease databases Malacards, MutationView, and Clinvar, and the functions and influences of the identified pathogenic genes were analyzed using statistical analysis and the gene enrichment approach.ResultsThrough GO enrichment analysis, it was found that the most significant gene ontology enrichment was the function “hormone activity” in terms of gene ontology molecular function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included TG, CALCA, POMC, CGA, PTH, GHRL, FBN1, TRH, PRL, LEP, ADIPOQ, INS, GH1. The second most significant gene ontology enrichment was the function “response to peptide hormone” in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included LRP6, TSC2, KANK1, COL1A1, CDKN1B, POMC, STAT1, MEN1, APC, GHRL, TSHR, GJB2, FBN1, GPT, LEP, ADIPOQ, INS, GH1. Through KEGG enrichment analysis, it was found that the most significant biological signaling pathway enrichment was the pathway “Thyroid hormone signaling pathway” function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included NOTCH3, MYH7, TSC2, STAT1, MED13L, MAP2K2, SLCO1C1, SLC16A2, and THRB. The second most significant biological signaling pathway enrichment was the pathway “Hypertrophic cardiomyopathy” in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included IGF1, CACNA1S, MYH7, IL6, TTN, CACNB2, LAMA2, and DMD.ConclusionThe mutated genes in children with hyperthyroidism were closely linked to function involved in “hormone activity” and “response to peptide hormone” in terms of the biological signaling pathway, and to the functional pathways involved in “Thyroid hormone signaling pathway” and “Hypertrophic cardiomyopathy” in terms of the biological signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Functional enrichment analysis of mutated genes in children with hyperthyroidism

Mao,

Tang,

et al. 2023

Front. Endocrinol.

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Clinical Study of Congenital Thyroid Dysfunction Caused by TSHR Gene Mutation

陈

2022

ACM

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Relationship between Mutant Genes, SNPs and Mutation Types in Children with Hyperthyroidism Based on Canonical correlation Analysis (Preprint)

Mao,

Tang,

et al. 2023

Preprint

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BACKGROUND Generally, different mutation types affect patients to various degrees. Some mutation types, such as synonymous mutations, do not cause changes in amino acid sequence and have little impact on patients. In contrast, some types of mutations will lead to wrong encoding or stop encoding of amino acid sequences, which will have a more significant impact on patients. OBJECTIVE Therefore, this paper intends to find the genetic characteristics of hyperthyroidism in children from the perspective of mutation types: missense mutations, synonymous mutations, nonsense mutations, and splice site mutations, and explore the relationship between mutant Genes, SNPs, and mutation types in patients. Finally, find the mutation type in which the specific mutant gene and the mutation site were biased. METHODS Use the canonical correlation analysis method to find the relationship between the mutant gene, the mutation site, and the mutation type. RESULTS Based on the complete linear correlation, single value, and Pearson correlation coefficient, screen the mutant genes and SNPs, then get 23 representative mutant genes from 144 mutant genes in 39 children and 8 representative SNPs from 1221 SNPs in 39 children. Canonical variables were constructed using data from representative mutant genes, SNPs, and their corresponding mutation types for canonical correlation analysis. A significant positive correlation between the mutant gene and the mutation type and a significant positive correlation between SNPs and the mutation type were found through canonical variable correlation and significance tests.The mutant genes for children with hyperthyroidism consist of 23 representative mutant genes, among which the genes ACADM, ATM, BARD1, CALCA, CAPN3, CRP, DNMT1, DNMT3A, FANCC, GHRL, KANK1, LRSAM1, TPO, TSHR, VWF are all prone to missense mutations, nonsense mutation, and synonymous mutation, the gene CGA is prone to splice site mutation. Among the 23 genes, the gene KANK1 has the greatest impact on the ensemble of mutant genes. SNPs for children with hyperthyroidism consist of 8 representative SNPs, among which g.1529224C>T, g.23019637C>G and g.44651599T>C are prone to missense mutations, g.1533961C>T, g.12718004G> A, g.43082453A>G, g.44652143G>A and g.71809992C>T are prone to synonymous mutations. The site g.44651599T>C has the greatest impact on the ensemble of SNPs. CONCLUSIONS There is a strong correlation between gene mutation types and mutant genes and between mutation types and SNPs in children with hyperthyroidism. Each mutant gene and SNP has a more preferred mutation type, among which gene CGA and gene KANK1 may be the mutant gene that has the most significant impact on children, and SNP g.44651599T>C may be the SNP that has the greatest impact on children.

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Utility of systematic TSHR gene testing in adults with hyperthyroidism lacking overt autoimmunity and diffuse uptake on thyroid scintigraphy

Cited by 3 publications

References 22 publications

Functional enrichment analysis of mutated genes in children with hyperthyroidism

Functional enrichment analysis of mutated genes in children with hyperthyroidism

Clinical Study of Congenital Thyroid Dysfunction Caused by TSHR Gene Mutation

Relationship between Mutant Genes, SNPs and Mutation Types in Children with Hyperthyroidism Based on Canonical correlation Analysis (Preprint)

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