Reduced L- and M- and increased S-cone functions in an infant with thyroid hormone resistance due to mutations in the THRβ2 gene.

Background: To document an infant with a cone photoreceptor disorder associated with severe thyroid hormone resistance due to compound heterozygosity in the thyroid hormone receptor beta 2 (TRβ2) encoding gene THRβ2.Materials and methods: Cone photoreceptor function was assessed using standard electroretinography (ERG) including colored flashes. We PCR-amplified and sequenced exons 8-10 of the THRβ2 gene. We cloned and sequenced a genomic segment (exons 9-10) of the THRβ2 gene to confirm a compound heterozygote mutation. We investigated whether mutations in the (OPN1LW-OPN1MW) gene array were responsible for the phenotype.Results: ERG testing showed a normal scotopic response and severely reduced photopic response. Spectral testing showed a small amplitude b-wave to a red flash and a larger amplitude b-wave to the blue flash. Molecular analysis revealed this child was a compound heterozygote for p.R338W and p.R429W mutations in exons 9 and 10 of the THRβ2 gene. These two mutations lie within the ligand-bi...