{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:25:01Z","timestamp":1791487501101,"version":"4.3.4"},"reference-count":83,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation Fighting Blindness","award":["CD-CL-0617-0727-HSC"],"award-info":[{"award-number":["CD-CL-0617-0727-HSC"]}]},{"name":"Vision Science Research Program, University of Toronto","award":["Graduate (MSc) student funding"],"award-info":[{"award-number":["Graduate (MSc) student funding"]}]},{"name":"Foundation Fighting Blindness","award":["CD-CMM-0224-0873-HSC"],"award-info":[{"award-number":["CD-CMM-0224-0873-HSC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,6]]},"abstract":"<jats:p>\n                    Hereditary macular dystrophies (HMDs) are a genetically diverse group of disorders that cause central vision loss due to photoreceptor and retinal pigment epithelium (RPE) damage. We investigated a family with a presumed novel autosomal-dominant HMD characterized by faint, hypopigmented RPE changes involving the central retina. Genome and RNA sequencing identified the disease-causing variant to be a 560 kb tandem duplication on chromosome 17 [NC_000017.10 (hg19): g.4012590_4573014dup], which led to the formation of a novel\n                    <jats:italic>ZZEF1-ALOX15<\/jats:italic>\n                    fusion gene, which upregulates\n                    <jats:italic>ALOX15<\/jats:italic>\n                    .\n                    <jats:italic>ALOX15<\/jats:italic>\n                    encodes a lipoxygenase involved in polyunsaturated fatty acid metabolism. Functional studies showed retinal disorganization and photoreceptor and RPE damage following electroporation of the chimera transcript in mouse retina. Photoreceptor damage also occurred following electroporation with a native\n                    <jats:italic>ALOX15<\/jats:italic>\n                    transcript but not with a near-null\n                    <jats:italic>ALOX15<\/jats:italic>\n                    transcript. Affected patients\u2019 lymphoblasts demonstrated lower levels of ALOX15 substrates and an accumulation of neutral lipids. We implicated the fusion gene as the cause of this family\u2019s HMD, due to mislocalization and overexpression of ALOX15, driven by the\n                    <jats:italic>ZZEF1<\/jats:italic>\n                    promoter. To our knowledge, this is the first reported instance of a fusion gene leading to HMD or inherited retinal dystrophy, highlighting the need to prioritize duplication analysis in unsolved retinal dystrophies.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178768","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T12:00:21Z","timestamp":1729598421000},"source":"Crossref","is-referenced-by-count":4,"title":["Autosomal-dominant macular dystrophy linked to a chromosome 17 tandem duplication"],"prefix":"10.1172","volume":"9","author":[{"given":"Rabiat","family":"Adele","sequence":"first","affiliation":[{"name":"Genetics & Genome Biology program, Hospital for Sick Children (HSC), Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowaida","family":"Hussein","sequence":"additional","affiliation":[{"name":"Genetics & Genome Biology program, Hospital for Sick Children (HSC), Toronto, Ontario, 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