{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T08:58:45Z","timestamp":1777193925477,"version":"3.51.4"},"reference-count":13,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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&gt;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.<\/jats:p>","DOI":"10.3390\/genes16101240","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:27:29Z","timestamp":1760963249000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mutation of the Thyroid Hormone Receptor Beta Gene (THRB) Causes Vitelliform Macular Dystrophy with High Intrafamilial Variability"],"prefix":"10.3390","volume":"16","author":[{"given":"Elisa A.","family":"Mahler","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"Ophthalmology Department, Necker Enfants Malades University Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Paris Cit\u00e9 University, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9330-9036","authenticated-orcid":false,"given":"Lars C.","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, Division of Laboratory Research, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3420-0054","authenticated-orcid":false,"given":"Katharina","family":"Wall","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5265-4645","authenticated-orcid":false,"given":"Marlene","family":"Sa\u00dfmannshausen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Kron","sequence":"additional","affiliation":[{"name":"Bioscientia Human Genetics, Institute for Medical Diagnostics GmbH, 55218 Ingelheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanno J.","family":"Bolz","sequence":"additional","affiliation":[{"name":"Bioscientia Human Genetics, Institute for Medical Diagnostics GmbH, 55218 Ingelheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank G.","family":"Holz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cremers, F.P.M., Boon, C.J.F., Bujakowska, K., and Zeitz, C. 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