Abstract
Purpose: :
To describe the first case of blue-cone monochromatism (BCM) in an infant with severe thyroid hormone resistance due to mutations in the gene (THRβ2) encoding thyroid hormone receptor beta 2 (Trβ2).
Methods: :
We PCR-amplified and directly sequenced exons 8-10 of the THRβ2 gene in a child with blue cone monochromacy documented by electroretinogram (ERG) testing including spectral stimuli.
Results: :
Molecular analysis revealed that the child is a compound heterozygote for p.R338W and p.R429W mutations in the THRβ2 gene. These two mutations lie within the ligand-binding domain but are known to selectively inhibit Trβ2 binding as homodimers to the thyroid hormone receptor response elements (TREs). ERG testing showed a reduced photopic response. Spectral testing on a white background showed a small amplitude b-wave (11 µV) to the red flash and a larger amplitude b-wave (31 µV) to the blue flash.
Conclusions: :
This report is the first to document BCM caused by deleterious mutations in the THRβ2 gene. Therefore, thyroid hormone, via TRβ2, is critical for middle-wave-sensitive (MWS) and long-wave-sensitive (LWS) cone development in the fovea and peripheral retina in humans.
Keywords: color pigments and opsins • retinal development • electroretinography: clinical