Search Results (4)

Background/Objectives: Herein, we report the clinical cases of two affected first-degree relatives from a family with highly variable macular dystrophy, expanding the known phenotype spectrum with mutations in the thyroid hormone receptor beta gene (THRB). Methods: Multimodal retinal imaging included wide-field fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) imaging, performed alongside functional testing (visual fields, electroretinogram (ERG)), metabolic blood analyses, and genetic testing of both cases. Results: A 67-year-old female patient presenting with reading difficulties and visual impairment since childhood was referred for evaluation and counseling for potential treatment options. Extensive ophthalmologic examination, including multimodal retinal imaging and functional testing, revealed an occult macular dystrophy. Her 39-year-old son reported similar visual symptoms in combination with mild photophobia. In multimodal retinal imaging, he also showed a macular dystrophy but with a vitelliform phenotype. Genetic testing identified the heterozygous pathogenic variant c.283+1G>A in the thyroid hormone receptor beta gene (THRB) in both patients. Conclusions: This report shows a high intrafamilial variability of macular dystrophy caused by a heterozygous THRB mutation, which has only recently been recognized as a cause of macular dystrophy. Here, we describe a novel clinical presentation characterized by a vitelliform lesion, expanding the phenotypic spectrum of THRB-associated macular dystrophy. Full article

During the early growth stages of fish larvae, there are significant challenges to their viability, so improving their visual environment is essential to promoting their growth and survival. Following the successful knockout of thyroid hormone receptor beta 2 (thrb2) using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, there was an increase in the expression of UV opsin (short-wave-sensitive 1, sws1), while the expression of other cone opsins was significantly decreased. Further analysis of the retinal structure demonstrated that the thrb2 knockout resulted in an increased lens thickness and a decreased thickness of the ganglion cell layer (GCL), outer plexiform layer (OPL), and outer nuclear layer (ONL) in the retina. The slowing down of swimming speed under light conditions in thrb2^−/− may be related to the decreased expression of phototransduction-related genes such as G protein-coupled receptor kinase 7a (grk7a), G protein-coupled receptor kinase 7b (grk7b), and phosphodiesterase 6c (pde6c). Notably, thrb2^−/− larvae exhibited a significant increase in the amount and proportion of first feeding, and their growth rate significantly exceeded that of wild-type controls during the week after feeding. This observation suggests that although the development of the retina may be somewhat affected, thrb2^−/− larvae show positive changes in feeding behaviour and growth rate, which may be related to their enhanced ability to adapt to their environment. These results provide novel insights into the function of the thrb2 gene in the visual system and behaviour and may have implications in areas such as fish farming and genetic improvement. Full article

The retina is crucial for converting light into neuronal signals for visual perception. Understanding the retina’s structure, function, and development is essential for vision research. It is known that the thyroid hormone (TH) receptor type beta 2 (TRβ2) is a key element in the regulation of cone differentiation in the retina, but other elements of TH signaling, such as transporters and enzyme deiodinases, have also been implicated in retinal cell development and survival. In the present study, we investigated the expression profile of genes involved in TH signaling and analyzed the impact of thyroidal status on retinal morphology, opsin expression, cell death/proliferation profile, as well as color preference behavior during the early retina development of zebrafish larvae. mRNA expression analysis on dissected whole eyes revealed that TH signaling elements gradually increase during eye development, with dio3b being the component that shows the most dramatic change. Mutations generated by CRISPR/CAS9 in the dio3b gene, but not in the thrb gene, modifies the structure of the retina. Disruption in TH level reduces the cell number of the ganglion cell layer, increases cell death, and modifies color preference, emphasizing the critical importance of precise TH regulation by its signaling elements for optimal retinal development and function. Full article

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta (THRB) gene is found. The clinical picture of RTHβ is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with THRB mutation (heterozygous disease-variant c.727C>T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTHβ. This is the first description of the known Slovenian cases with RTHβ due to the pathogenic mutation in the THRB gene. Hypercholesterolemia might be etiologically related with RTHβ, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with THRB variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTHβ patients. Full article