{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:13:43Z","timestamp":1792512823872,"version":"4.5.0"},"reference-count":9,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["M2R202106013619"],"award-info":[{"award-number":["M2R202106013619"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR10\u2010IAHU\u201001"],"award-info":[{"award-number":["ANR10\u2010IAHU\u201001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Whole\u2010genome sequencing (WGS) now allows identification of multiple variants in non\u2010coding regions. The large number of variants identified by WGS however complicates their interpretation. Through identification of the first deep intronic variant in\n                    <jats:italic>NPHS2<\/jats:italic>\n                    , which encodes podocin, a protein implicated in autosomal recessive steroid resistant nephrotic syndrome (SRNS), we compare herein three different tools including a newly developed targeted NGS\u2010based RNA\u2010sequencing to explore the splicing effect of intronic variations.\n                  <\/jats:p>\n                  <jats:p>\n                    WGS identified two different variants in\n                    <jats:italic>NPHS2<\/jats:italic>\n                    eventually involved in the disease. Through RT\u2010PCR, exon\u2010trapping Minigene assay and targeted RNA sequencing, we were able to identify the splicing defect in\n                    <jats:italic>NPHS2<\/jats:italic>\n                    mRNA from patient kidney tissue. Only targeted RNA\u2010seq simultaneously analyzed the effect of multiple variants and offered the opportunity to quantify consequences on splicing. Identifying deep intronic variants and their role in disease is of utmost importance. Alternative splicing can be predicted by in silico tools but always requires confirmation through functional testing with RNA analysis from the implicated tissue remaining the gold standard. When several variants with potential effects on splicing are identified by WGS, a targeted RNA sequencing panel could be of great value.\n                  <\/jats:p>","DOI":"10.1111\/cge.14305","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T08:43:55Z","timestamp":1674809035000},"page":"693-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Overcoming the challenges associated with identification of deep intronic variants by whole genome sequencing"],"prefix":"10.1111","volume":"103","author":[{"given":"Marie","family":"Dirix","sequence":"first","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gribouval","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Arrondel","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadia","family":"Benjelloun","sequence":"additional","affiliation":[{"name":"Laboratoires de biologie m\u00e9dicale SeqOIA  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Boyer","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte MARHEA H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Charbit","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte MARHEA H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Antignac","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"},{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares, APHP Universit\u00e9 Paris\u2010Cit\u00e9  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-5515","authenticated-orcid":false,"given":"Laurence","family":"Heidet","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l'Enfant et de l'Adulte MARHEA H\u00f4pital Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Dorval","sequence":"additional","affiliation":[{"name":"INSERM U1163, Laboratoire des Maladies R\u00e9nales H\u00e9r\u00e9ditaires, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  France"},{"name":"Service de M\u00e9decine G\u00e9nomique des Maladies Rares, APHP Universit\u00e9 Paris\u2010Cit\u00e9  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.13371019"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014050489"},{"issue":"12","key":"e_1_2_10_4_1","first-page":"2675","article-title":"The missing puzzle piece: splicing mutations","volume":"6","author":"Lewandowska MA","year":"2013","journal-title":"Int J Clin Exp 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