Congenital hypothyroidism

Gene: TRHR

Green List (high evidence)

TRHR (thyrotropin releasing hormone receptor)
EnsemblGeneIds (GRCh38): ENSG00000174417
EnsemblGeneIds (GRCh37): ENSG00000174417
OMIM: 188545, Gene2Phenotype
TRHR is in 3 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green: 1 Green review (by gene submitter) plus 3 unrelated cases.
Created: 16 Feb 2017, 2:41 p.m.
PMID:26735259 (Koulouri et al., 2016) provides a 3rd case: a homozygous P81R mutation in a female patient with isolated central congenital hypothyroidism (CCH), together with functional studies of the mutated protein.
Created: 16 Feb 2017, 2:40 p.m.
PMID:19213692 (Bonomi et al., 2009) report on a family with recessive resistance to the action of thyrotropin-releasing hormone (TRH) due to a nonsense homozygous mutation in the TRH receptor (TRHR) gene (p.R17X). Idiopathic and isolated hypothyroidism was diagnosed in the proband. The proband's apparently asymptomatic 33-year-old sister was also homozygous for the mutation; she had never had manifestations of hypothyroidism, but reported substantial improvement in physical and mental activities after receiving thyroxine-replacement therapy.
Created: 16 Feb 2017, 2:36 p.m.
In a 9-year-old Caucasian boy with isolated central hypothyroidism, Collu et al. (1997, PMID:9141550) identified compound heterozygosity for mutations in the TRHR gene.
Created: 16 Feb 2017, 2:34 p.m.

Nadia Schoenmakers (University of Cambridge)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
mild-moderate isolated central hypothyroidism; absent TSH and prolactin response to TRH

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • mild-moderate isolated central hypothyroidism
  • absent TSH and prolactin response to TRH
  • Thyrotropin-releasing hormone resistance, generalized
OMIM
188545
Clinvar variants
Variants in TRHR
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

22 Feb 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.

16 Feb 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

14 Feb 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for TRHR were set to mild-moderate isolated central hypothyroidism; absent TSH and prolactin response to TRH; Thyrotropin-releasing hormone resistance, generalized

11 Feb 2017, Gel status: 0

Added New Source

Nadia Schoenmakers (University of Cambridge)

TRHR was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Literature

11 Feb 2017, Gel status: 0

Created

Nadia Schoenmakers (University of Cambridge)

TRHR was created by [email protected]