{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:59:58Z","timestamp":1783713598381,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS098004"],"award-info":[{"award-number":["R01NS098004"]}],"id":[{"id":"10.13039\/100000002","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":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the <jats:italic>CAPN15<\/jats:italic> gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in <jats:italic>CAPN15<\/jats:italic> with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy\u2013Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with <jats:italic>CAPN15<\/jats:italic>\u2010related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy\u2013Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy\u2013Walker malformation with biallelic <jats:italic>CAPN15<\/jats:italic> variants, thereby expanding the neurologic spectrum among patients affected by <jats:italic>CAPN15<\/jats:italic>\u2010related disease.<\/jats:p>","DOI":"10.1002\/ajmg.a.63363","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T20:21:25Z","timestamp":1692649285000},"page":"2757-2767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel association of Dandy\u2013Walker malformation with <scp><i>CAPN15<\/i><\/scp> variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4066-2060","authenticated-orcid":false,"given":"M. Makenzie","family":"Beaman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics Duke University  Durham North Carolina USA"},{"name":"Medical Scientist Training Program Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Guidugli","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9693-2459","authenticated-orcid":false,"given":"Monia","family":"Hammer","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Barrows","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"},{"name":"Laboratory for Pediatric Brain Disease University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9166-6593","authenticated-orcid":false,"given":"Anne","family":"Gregor","sequence":"additional","affiliation":[{"name":"Laboratory for Pediatric Brain Disease University of California San Diego  La Jolla California USA"},{"name":"Department of Human Genetics Inselspital Bern, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7723-5946","authenticated-orcid":false,"given":"Sangmoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"},{"name":"Laboratory for Pediatric Brain Disease University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-6326","authenticated-orcid":false,"given":"Kristen L.","family":"Deak","sequence":"additional","affiliation":[{"name":"Department of Pathology Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-8486","authenticated-orcid":false,"given":"Marie T.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-9899","authenticated-orcid":false,"given":"Courtney","family":"Jensen","sequence":"additional","affiliation":[{"name":"Children's Services, Duke University Health Center, Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-0002","authenticated-orcid":false,"given":"Maha S.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Clinical Genetics Department Human Genetics and Genome Research Institute, National Research Centre  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-8713","authenticated-orcid":false,"given":"Amira T.","family":"Masri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Child Neurology University of Jordan  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-5952","authenticated-orcid":false,"given":"Charlotte A.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-9220","authenticated-orcid":false,"given":"Joseph G.","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Rady Children's Hospital  San Diego California USA"},{"name":"Laboratory for Pediatric Brain Disease University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-1025","authenticated-orcid":false,"given":"Jennifer L.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00872-y"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1105"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(84)90050-2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24309"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02355-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14473"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.020"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5395"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.08.009"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.11.032"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13920"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx439"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.097857.109"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a005470"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3715005"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.87.287"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a002519"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37225"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.04.023"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa198"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T06:12:08Z","timestamp":1697263928000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,19]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/ajmg.a.63363"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63363","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,19]]},"assertion":[{"value":"2023-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}