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Med."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in\n                    <jats:italic>INPP5E<\/jats:italic>\n                    cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in\n                    <jats:italic>INPP5E<\/jats:italic>\n                    . Additional two patients showed early onset IRD with limited JBTS features. Detailed phenotypic description for all probands is presented. We report 14 rare\n                    <jats:italic>INPP5E<\/jats:italic>\n                    variants, 12 of which have not been reported in previous studies. We present tertiary protein modeling and analyze all\n                    <jats:italic>INPP5E<\/jats:italic>\n                    variants for deleteriousness and phenotypic correlation. We observe that the combined impact of\n                    <jats:italic>INPP5E<\/jats:italic>\n                    variants in JBTS and non-syndromic IRD patients does not reveal a clear genotype\u2013phenotype correlation, suggesting the involvement of genetic modifiers. Our study cements the wide phenotypic spectrum of\n                    <jats:italic>INPP5E<\/jats:italic>\n                    disease, adding proof that sequence defects in this gene can lead to early-onset non-syndromic IRD.\n                  <\/jats:p>","DOI":"10.1038\/s41525-021-00214-8","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T06:06:39Z","timestamp":1624946799000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD"],"prefix":"10.1038","volume":"6","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":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-8133","authenticated-orcid":false,"given":"Erin","family":"Zampaglione","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":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9897-4561","authenticated-orcid":false,"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":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-2431","authenticated-orcid":false,"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":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-9950","authenticated-orcid":false,"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":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9220-2261","authenticated-orcid":false,"given":"Rachel M.","family":"Huckfeldt","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-9818","authenticated-orcid":false,"given":"Kinga M.","family":"Bujakowska","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"214_CR1","unstructured":"Daiger S. 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