{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:41:25Z","timestamp":1790692885885,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T00:00:00Z","timestamp":1683936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"FRM","doi-asserted-by":"publisher","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"FRM","doi-asserted-by":"publisher","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation JED-Belgique","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}]},{"name":"Fondation JED-Belgique","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}]},{"name":"EJP RD Solve-RET","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}]},{"name":"EJP RD Solve-RET","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}]},{"name":"Agence de la Biom\u00e9decine","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}]},{"name":"Agence de la Biom\u00e9decine","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}]},{"name":"University of Strasbourg and Strasbourg University Hospital","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}]},{"name":"University of Strasbourg and Strasbourg University Hospital","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}]},{"name":"La Fondation Maladie Rare","award":["ECO20170637509"],"award-info":[{"award-number":["ECO20170637509"]}]},{"name":"La Fondation Maladie Rare","award":["EJPRD19-234"],"award-info":[{"award-number":["EJPRD19-234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bardet\u2013Biedl syndrome (BBS) is an autosomal recessive ciliopathy that affects multiple organs, leading to retinitis pigmentosa, polydactyly, obesity, renal anomalies, cognitive impairment, and hypogonadism. Until now, biallelic pathogenic variants have been identified in at least 24 genes delineating the genetic heterogeneity of BBS. Among those, BBS5 is a minor contributor to the mutation load and is one of the eight subunits forming the BBSome, a protein complex implied in protein trafficking within the cilia. This study reports on a European BBS5 patient with a severe BBS phenotype. Genetic analysis was performed using multiple next-generation sequencing (NGS) tests (targeted exome, TES and whole exome, WES), and biallelic pathogenic variants could only be identified using whole-genome sequencing (WGS), including a previously missed large deletion of the first exons. Despite the absence of family samples, the biallelic status of the variants was confirmed. The BBS5 protein\u2019s impact was confirmed on the patient\u2019s cells (presence\/absence and size of the cilium) and ciliary function (Sonic Hedgehog pathway). This study highlights the importance of WGS and the challenge of reliable structural variant detection in patients\u2019 genetic explorations as well as functional tests to assess a variant\u2019s pathogenicity.<\/jats:p>","DOI":"10.3390\/ijms24108729","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T02:56:57Z","timestamp":1684119417000},"page":"8729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["WGS Revealed Novel BBS5 Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects"],"prefix":"10.3390","volume":"24","author":[{"given":"Adella","family":"Karam","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Delvall\u00e9e","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-2465","authenticated-orcid":false,"given":"Alejandro","family":"Estrada-Cuzcano","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Geoffroy","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Baptiste","family":"Lamouche","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Leuvrey","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Nourisson","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Tarabeux","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Stoetzel","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-559X","authenticated-orcid":false,"given":"Jean","family":"Muller","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique M\u00e9dicale, UMR_S INSERM U1112, Institut de G\u00e9n\u00e9tique M\u00e9dicale d\u2019Alsace (IGMA), Facult\u00e9 de M\u00e9decine FMTS, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"},{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"},{"name":"Unit\u00e9 Fonctionnelle de Bioinformatique M\u00e9dicale Appliqu\u00e9e au Diagnostic (UF7363), H\u00f4pitaux Universitaires de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00467-010-1731-7","article-title":"Ciliopathies: An Expanding Disease Spectrum","volume":"26","author":"Waters","year":"2011","journal-title":"Pediatr. 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