{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:34:24Z","timestamp":1768548864922,"version":"3.49.0"},"posted":{"date-parts":[[2020,8,26]]},"group-title":"Genetic and Genomic Medicine","reference-count":40,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,8,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in\n                    <jats:italic>INPP5E<\/jats:italic>\n                    cause Joubert syndrome, a systemic disorder that can manifest with retinal degeneration among other clinical features. We aimed to evaluate the role of\n                    <jats:italic>INPP5E<\/jats:italic>\n                    variants in non-syndromic inherited retinal degenerations (IRDs) of varying severity.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Targeted or genome sequencing were performed in 12 unrelated non-syndromic IRD families from multiple research hospitals. Detailed clinical examination was conducted in all probands. The impact of new likely pathogenic variants was modeled on a tertiary INPP5E protein structure and all the new and published variants were analyzed for their deleteriousness and phenotypic correlation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Fourteen\n                    <jats:italic>INPP5E<\/jats:italic>\n                    rare alleles were detected, 12 of which were novel. Retinal degeneration in all 12 probands was clinically distinguishable on the basis of onset and severity into Leber congenital amaurosis (n=4) and a milder, later-onset rod-cone dystrophy (n=8). Two probands showed mild ciliopathy features that resolved in childhood. Analysis of the combined impact of both alleles in syndromic and non-syndromic\n                    <jats:italic>INPP5E<\/jats:italic>\n                    patients did not reveal clear genotype-phenotype correlation, suggesting involvement of genetic modifiers.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    The study expands the phenotypic spectrum of disorders due to pathogenic variants in\n                    <jats:italic>INPP5E<\/jats:italic>\n                    and describes a new disease association with previously underdiagnosed forms of early-onset non-syndromic IRD.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2020.08.24.20179085","type":"posted-content","created":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T03:15:13Z","timestamp":1598498113000},"source":"Crossref","is-referenced-by-count":1,"title":["Early onset non-syndromic retinal degeneration due to variants in\n                  <i>INPP5E:<\/i>\n                  phenotypic expansion of the ciliary gene previously associated with Joubert syndrome"],"prefix":"10.64898","author":[{"given":"Riccardo","family":"Sangermano","sequence":"first","affiliation":[]},{"given":"Iris","family":"Deitch","sequence":"additional","affiliation":[]},{"given":"Virginie G.","family":"Peter","sequence":"additional","affiliation":[]},{"given":"Rola","family":"Ba-Abbad","sequence":"additional","affiliation":[]},{"given":"Emily M.","family":"Place","sequence":"additional","affiliation":[]},{"given":"Naomi E.","family":"Wagner","sequence":"additional","affiliation":[]},{"given":"Anne B.","family":"Fulton","sequence":"additional","affiliation":[]},{"given":"Luisa","family":"Coutinho-Santos","sequence":"additional","affiliation":[]},{"given":"Boris","family":"Rosin","sequence":"additional","affiliation":[]},{"given":"Vincent","family":"Dunet","sequence":"additional","affiliation":[]},{"given":"Ala\u2019a","family":"AlTalbishi","sequence":"additional","affiliation":[]},{"given":"Eyal","family":"Banin","sequence":"additional","affiliation":[]},{"given":"Ana Berta","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Mariana","family":"Neves","sequence":"additional","affiliation":[]},{"given":"Anna","family":"Larson","sequence":"additional","affiliation":[]},{"given":"Mathieu","family":"Quinodoz","sequence":"additional","affiliation":[]},{"given":"Michel","family":"Michaelides","sequence":"additional","affiliation":[]},{"given":"Tamar","family":"Ben-Yosef","sequence":"additional","affiliation":[]},{"given":"Eric A.","family":"Pierce","sequence":"additional","affiliation":[]},{"given":"Carlo","family":"Rivolta","sequence":"additional","affiliation":[]},{"given":"Andrew R.","family":"Webster","sequence":"additional","affiliation":[]},{"given":"Gavin","family":"Arno","sequence":"additional","affiliation":[]},{"given":"Dror","family":"Sharon","sequence":"additional","affiliation":[]},{"given":"Rachel M.","family":"Huckfeldt","sequence":"additional","affiliation":[]},{"given":"Kinga M.","family":"Bujakowska","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2021020311450927000_2020.08.24.20179085v1.1","unstructured":"Retinal Information Network (RetNet). https:\/\/sph.uth.edu\/retnet\/home.htm. 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