# Mutation of the Thyroid Hormone Receptor Beta Gene (THRB) Causes Vitelliform Macular Dystrophy with High Intrafamilial Variability

## TL;DR

A mutation in the THRB gene causes a type of eye disease called vitelliform macular dystrophy, with varying symptoms among family members.

## Contribution

This study expands the known clinical spectrum of THRB-associated macular dystrophy by identifying a novel vitelliform phenotype.

## Key findings

- A heterozygous THRB mutation (c.283+1G>A) was found in two family members with distinct macular dystrophy presentations.
- The younger patient showed a vitelliform macular dystrophy phenotype, while the older patient had an occult form.
- THRB mutations are now associated with high intrafamilial variability in macular dystrophy symptoms.

## Abstract

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.