Details of Disease

General Information of Disease (ID: DIS4TOK0)

• Disease Name: Generalized resistance to thyroid hormone
• Synonyms: deafness-thyroid hormone resistance syndrome; Refetoff syndrome; GRTH
• Definition: A thyroid hormone resistance syndrome characterized by resistance in the pituitary gland and in most or all of the peripheral tissues.
• Disease Hierarchy:
  DISX87ZH: Hyperthyroidism
  :
  DIS4TOK0: Generalized resistance to thyroid hormone
• Disease Identifiers:
  MONDO ID: MONDO_0009043
  MESH ID: D018382
  UMLS CUI: C4722330
  MedGen ID: 1654700
  HPO ID: HP:0002930
  Orphanet ID: 3221
  SNOMED CT ID: 237560005

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
TRB	TT84HCW	Disputed	Genetic Variation	[1]
THRA	TTTSEPU	Strong	Genetic Variation	[2]
TRH	TT2Z39D	Strong	Biomarker	[3]
TRHR	TT4J8MF	Strong	Biomarker	[4]
TSHR	TT6NYJA	Strong	Genetic Variation	[5]
FGR	TTPOGS1	Definitive	Biomarker	[6]
NR1D1	TTAD1O8	Definitive	Genetic Variation	[7]
RXRG	TTH029C	Definitive	Genetic Variation	[8]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC16A2	DTQ8MP1	Strong	Biomarker	[9]

This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NCOR1	OT04XNOU	Limited	Biomarker	[6]
DDX25	OTF36NBP	Disputed	Biomarker	[10]
NCOR2	OTY917X0	Disputed	Biomarker	[11]
TSHB	OTFDI39D	Disputed	Biomarker	[12]
NCOA1	OTLIUJQD	moderate	Biomarker	[6]
LCOR	OT1K7DKB	Definitive	Biomarker	[13]
THRSP	OTKYE01L	Definitive	Biomarker	[14]

References

• [1] T426I a new mutation in the thyroid hormone receptor beta gene in a sporadic patient with resistance to thyroid hormone and dysmorphism. Mutations in brief no. 192. Online.Hum Mutat. 1998;12(4):289.
• [2] A novel thyroid hormone receptor alpha gene mutation, clinic characteristics, and follow-up findings in a patient with thyroid hormone resistance.Hormones (Athens). 2019 Jun;18(2):223-227. doi: 10.1007/s42000-019-00094-9. Epub 2019 Feb 12.
• [3] Challenging diagnosis of resistance to thyroid hormone in a patient with pituitary adenoma.BMJ Case Rep. 2019 Jul 19;12(7):e229430. doi: 10.1136/bcr-2019-229430.
• [4] A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene.J Clin Endocrinol Metab. 1997 May;82(5):1561-5. doi: 10.1210/jcem.82.5.3918.
• [5] DUOX2 Gene Mutation Manifesting as Resistance to Thyrotropin Phenotype.Thyroid. 2017 Jan;27(1):129-131. doi: 10.1089/thy.2016.0469. Epub 2016 Dec 7.
• [6] Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors.Mol Cell Biol. 2014 May;34(9):1564-75. doi: 10.1128/MCB.00129-14. Epub 2014 Feb 18.
• [7] Hippocampal Transcriptome Profile of Persistent Memory Rescue in a Mouse Model of THRA1 Mutation-Mediated Resistance to Thyroid Hormone.Sci Rep. 2016 Jan 8;6:18617. doi: 10.1038/srep18617.
• [8] Search for genetic variants in the retinoid X receptor-gamma-gene by polymerase chain reaction-single-strand conformation polymorphism in patients with resistance to thyroid hormone without mutations in thyroid hormone receptor beta gene.Thyroid. 2004 May;14(5):355-8. doi: 10.1089/105072504774193177.
• [9] Variable Clinical Characteristics and Molecular Spectrum of Patients with Syndromes of Reduced Sensitivity to Thyroid Hormone: Genetic Defects in the THRB and SLC16A2 Genes.Horm Res Paediatr. 2018;90(5):283-290. doi: 10.1159/000493468. Epub 2018 Nov 29.
• [10] Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone.J Clin Invest. 1993 May;91(5):2296-300. doi: 10.1172/JCI116458.
• [11] Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes.J Clin Endocrinol Metab. 2000 Oct;85(10):3609-17. doi: 10.1210/jcem.85.10.6873.
• [12] Evidence for the secretion of thyrotropin with enhanced bioactivity in syndromes of thyroid hormone resistance.J Clin Endocrinol Metab. 1994 May;78(5):1034-9. doi: 10.1210/jcem.78.5.8175956.
• [13] Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain.Mol Endocrinol. 2003 Jan;17(1):107-16. doi: 10.1210/me.2002-0097.
• [14] Thyroid Hormone Resistance in children.Pediatr Endocrinol Rev. 2003 Dec;1 Suppl 2:191-8; discussion 198.