{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:34:20Z","timestamp":1763552060952,"version":"3.41.2"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,20]],"date-time":"2020-06-20T00:00:00Z","timestamp":1592611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Retinitis pigmentosa (RP) is one of the most common form of inherited retinal dystrophies. Identification of disease\u2010causing mutations is a prerequisite for applying targeted therapeutic approaches. The present study aimed to identify disease\u2010associated mutations in a large Serbian family, in which two brothers have suffered from RP starting in the first decade of their lives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The index patient and 12 additional members of a four\u2010generation family were analyzed. All participants underwent detailed ophthalmic examinations. Genomic DNA was isolated from family members to perform whole exome sequencing (WES) and Sanger sequencing of candidate genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An early onset RP phenotype was presented in both ocular fundi of the index patient and his brother: arteriolar attenuation, as well as retinal pigmentary changes in peripheral fundus and waxy disc pallor. Both brothers showed foveal thinning. The index patient showed epiretinal membranes in both eyes and a parafoveal cystic lesion in his right eye, whereas the brother of the index patient showed choroid folds and vitreomacular adhesion in his left eye. We identified compound heterozygous mutations in the <jats:italic>RPE65<\/jats:italic> gene (a novel c.1338+1G&gt;A splice donor site mutation in addition to the frame\u2010shifting mutation c.1207_1210dup (p.Glu404Alafs*4)) using an in\u2010house WES pipeline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Evaluation of all previously described <jats:italic>RPE65<\/jats:italic> mutations showed that the sequence variants identified in the present study located to rarely altered exons and likely effect a highly conserved region of the RPE65 protein. Gene augmentation therapies might be a promising treatment option for the patients described.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3211","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T06:10:17Z","timestamp":1588659017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Compound heterozygous <i>RPE65<\/i> mutations associated with an early onset autosomal recessive retinitis pigmentosa"],"prefix":"10.1002","volume":"22","author":[{"given":"Marta","family":"Owczarek\u2010Lipska","sequence":"first","affiliation":[{"name":"Human Genetics, Faculty VI \u2010 School of Medicine and Health Sciences University of Oldenburg  Oldenburg Germany"},{"name":"Junior Research Group, Genetics of Childhood Brain Malformations Faculty VI \u2010 School of Medicine and Health Sciences, University of Oldenburg  Oldenburg 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