Retinal disorders

Gene: THRB

Green List (high evidence)

North Thames GLH Rare & Inherited Disease Laboratory WGS and 100K Diagnostic Discovery patients:
NM_001354712.2:c.283G>C p.(Gly95Arg) variant detected in 5 probands affected with retinal dystrophy in our patient cohort, segregating in affected relatives in 3 families. Total of affected individuals tested: 8.Thyroid features (hypothyroidism or Hashimoto's thyroiditis) reported in 2.
NM_001354712.2:c.283+1G>C also detected in proband and father affected with retinal dystrophy
both variants located in the same splice region and predicted to have the same effect as the reported c.283+1G>A in PMID 37547476

Created: 27 Mar 2025, 5:21 p.m. | Last Modified: 27 Mar 2025, 5:21 p.m.

Panel Version: 7.21

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
inherited retinal dystrophy, MONDO:0019118

Publications

• 37547476

Mode of pathogenicity
Other

Green List (high evidence)

Comment on list classification: As reviewed by Romana Izakovicova, a new variant (c.283G>C p.(Gly95Arg)) was reported in five probands from her clinical practice and 100k diagnostic discovery patients. Hence, there is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.

Created: 26 Apr 2025, 6:33 p.m. | Last Modified: 26 Apr 2025, 6:33 p.m.

Panel Version: 7.26

Comment on list classification: Although there are three unrelated cases, all of them were identified with the same variant and this variant has not yet been functionally characterised. Hence, this gene should be rated amber with current evidence.

The 'watchlist' tag has also been added.

Created: 18 Jun 2024, 2:37 p.m. | Last Modified: 18 Jun 2024, 2:37 p.m.

Panel Version: 5.11

PMID:37547476 reported a family of Spanish decent with autosomal dominant inherited retinal dystrophy (IRD) and monoallelic THRB variant (c.283 + 1G>A). An expanded genetic analysis of the THRB gene in an unsolved IRD cohort also resulted in the identification of the same variant in two additional unrelated families. There are also several studies that have shown a role for THRB gene in cone development in a wide range of model organisms.
Sources: Literature

Created: 18 Jun 2024, 2:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
inherited retinal dystrophy, MONDO:0019118

Publications

• 37547476