{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:40:04Z","timestamp":1783665604326,"version":"3.55.0"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Low\u2010density lipoprotein receptor\u2010related protein 6 (\n                    <jats:italic>LRP6<\/jats:italic>\n                    ) is a co\u2010receptor of the Wnt signaling pathway, which plays an essential role in various biological activities during embryonic and postnatal development.\n                    <jats:italic>LRP6<\/jats:italic>\n                    is exceptionally associated with rare diseases and always with autosomal dominant inheritance. Here we report a familial phenotype of high bone mass associated with skeletal anomalies and oligodontia but also persistent left superior vena cava, inguinal hernia, hepatic cysts, abnormal posterior fossa and genital malformations. Molecular analysis revealed a novel heterozygous variant, NM_002336.2: c.724T&gt;C, p.(Trp242Arg), in affected individuals. This variant is located in the first \u03b2\u2010propellant motif of\n                    <jats:italic>LRP6<\/jats:italic>\n                    , to which sclerostin (\n                    <jats:italic>SOST<\/jats:italic>\n                    ) and dickkopf1 (\n                    <jats:italic>DKK1<\/jats:italic>\n                    ), two\n                    <jats:italic>LRP6<\/jats:italic>\n                    co\u2010receptor inhibitors and various Wnt ligands bind. According to the literature and integrating data from structural analysis, this variant distorts the binding of\n                    <jats:italic>SOST<\/jats:italic>\n                    and\n                    <jats:italic>DKK1<\/jats:italic>\n                    , thus leading to overactivation of Wnt signaling pathways involved in osteoblast differentiation. This novel heterozygous variant in\n                    <jats:italic>LRP6<\/jats:italic>\n                    underlies the role of\n                    <jats:italic>LRP6<\/jats:italic>\n                    in skeletal and dental disorders as well as, probably, cardiac, cerebral and genital developments.\n                  <\/jats:p>","DOI":"10.1111\/cge.14501","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T10:40:27Z","timestamp":1708598427000},"page":"666-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel variant in\n                    <i>LRP6<\/i>\n                    associated with unusual and severe clinical presentation: Case report"],"prefix":"10.1111","volume":"105","author":[{"given":"Ana\u00efk","family":"Previdi","sequence":"first","affiliation":[{"name":"UFR de Pharmacie Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christ\u00e8le","family":"Dubourg","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire CHU Rennes, H\u00f4pital Sud, CLAD Ouest  Rennes France"},{"name":"Laboratoire de Biologie M\u00e9dicale Multisites Seqoia\u2010FMG2025  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Cormier Daire","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9nomique, INSERM UMR1163, Institut Imagine CHU Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Fradin","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique CHU Rennes, H\u00f4pital Sud, CLAD Ouest  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Collet","sequence":"additional","affiliation":[{"name":"UFR de Pharmacie Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Laboratoire de Biologie M\u00e9dicale Multisites Seqoia\u2010FMG2025  Paris France"},{"name":"D\u00e9partement de G\u00e9nomique, INSERM UMR1163, Institut Imagine CHU Necker\u2010Enfants Malades  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2019.05.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115550"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115706"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023537"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063323"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.670960"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01137"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13010120"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1136370"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10717"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00165"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2011.07.005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2706"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.092130"},{"key":"e_1_2_9_16_1","article-title":"LRP6 acts as a scaffold protein in cardiac gap junction assembly","volume":"7","author":"Li J","year":"2016","journal-title":"Nat Commun"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.714330"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T21:36:29Z","timestamp":1714599389000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,22]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/cge.14501"],"URL":"https:\/\/doi.org\/10.1111\/cge.14501","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14501\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14501\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14501\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14501\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14501\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14501\/v2\/review1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,22]]},"assertion":[{"value":"2023-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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