{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:33:13Z","timestamp":1778621593858,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2010syndromic Retinitis Pigmentosa (NsRP) was well known as one of the causes of visual impairment already in the 19th century. Giuseppe Albertotti, Professor of Ophthalmology at the University of Modena (Italy) in 1893, described a high prevalence of NsRP in a geographic isolate, the small village of Colloro, in northwestern Italy. In two living descendants, similarly affected with NsRP, we identified pathogenic variants in the\n                    <jats:italic>CRB1<\/jats:italic>\n                    gene as the cause of the visual impairment. Reconstruction of an extended pedigree demonstrated that all affected subjects go back to a single couple married in Colloro in the early 17th century and confirmed an autosomal recessive pattern of inheritance of the disease in this population. We also provide structural data on the novel\n                    <jats:italic>CRB1<\/jats:italic>\n                    pathogenic variant.\n                    <jats:italic>CRB1<\/jats:italic>\n                    , is a transmembrane protein primarily expressed in the retina, which plays a pivotal role in photoreceptor survival and maintaining retinal architecture. Pathogenic variants in the\n                    <jats:italic>CRB1<\/jats:italic>\n                    gene are associated with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), highlighting its significance in retinal health as these pathogenic variants lead to photoreceptor degeneration and progressive vision loss.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64161","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T05:50:35Z","timestamp":1750657835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Pathogenic Variant in\n                    <scp>\n                      <i>CRB1<\/i>\n                    <\/scp>\n                    as the Cause of Non\u2010Syndromic Retinitis Pigmentosa in a Geographical Isolate in Northern Italy"],"prefix":"10.1002","volume":"197","author":[{"given":"Andrea","family":"Guala","sequence":"first","affiliation":[{"name":"SOC Pediatria Ospedale Castelli  Verbania Verbania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-2023","authenticated-orcid":false,"given":"Fabio","family":"Sirchia","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Medical Genetics Unit IRCCS San Matteo Foundation  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Scotti","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Unit\u00e0 di Immunologia e Patologia Generale University of Pavia  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9152-435X","authenticated-orcid":false,"given":"Elena","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Falcioni","sequence":"additional","affiliation":[{"name":"Gruppo Genealogico Premosellese  Verbania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvano","family":"Ragozza","sequence":"additional","affiliation":[{"name":"Gruppo Genealogico Premosellese  Verbania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Casella","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Neurogenetics Research Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-6820","authenticated-orcid":false,"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Medical Genetics Unit, Neurogenetics Research Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8400-5671","authenticated-orcid":false,"given":"Cesare","family":"Danesino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23626"},{"key":"e_1_2_8_3_1","volume-title":"I Ciechi di Colloro Prolusion for the Academic Year 1893\u201394 at the Medical Faculty of the University of Modena","author":"Albertotti G.","year":"1893"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.06.033"},{"key":"e_1_2_8_5_1","volume-title":"Personal Communication, September 2023. Biomedical Research Institute Fundaci\u00f3n Jimenez Diaz","author":"Ayuso Garcia C.","year":"2023"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1510"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.42"},{"issue":"3","key":"e_1_2_8_8_1","first-page":"1","article-title":"Recommendations for Application of the Functional Evidence PS3\/BS3 Criterion Using the ACMG\/AMP Sequence Variant Interpretation Framework","volume":"12","author":"Brnich S. 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