{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:05:01Z","timestamp":1788609901588,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011775","name":"BC Children\u2019s Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011775","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Carpenter syndrome type 2 (CRPT2) is a rare autosomal recessive disease mainly characterized by craniosynostosis and polysyndactyly. CRPT2 is the rarer subtype of Carpenter syndrome (CRPTS) and is caused by biallelic variants in the multiple epidermal growth factor\u2010like domains 8 gene (\n                    <jats:italic>MEGF8<\/jats:italic>\n                    ). Due to its rarity and phenotypic overlap with other craniosynostosis syndromes, definitive molecular diagnosis of CRPT2 can be challenging. Here, we describe a proband with CRPT2 carrying compound heterozygous variants in\n                    <jats:italic>MEGF8<\/jats:italic>\n                    : one de novo variant disrupting splicing and a maternally inherited missense variant. To resolve these variants, we leveraged long\u2010read genome sequencing to phase the missense variant alleles and RNA sequencing to determine splicing impact. This case highlights the diagnostic value of using sequencing methods beyond the more conventional short\u2010read exome sequencing. Our findings expand the spectrum of\n                    <jats:italic>MEGF8<\/jats:italic>\n                    variants causing CRPT2 and underscore the utility of emerging sequencing technologies in elucidating complex or previously unresolved genotypes. Expanding access to such technologies is anticipated to accelerate rare disease diagnosis and deepen our understanding of the genetic mechanisms underlying these conditions.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70124","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T04:00:44Z","timestamp":1773460844000},"page":"1719-1724","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Combined Long\u2010Read Genome and Transcriptome Sequencing Establishes Novel Variants in\n                    <i>MEGF8<\/i>\n                    as the Cause for Carpenter Syndrome Type 2"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3621-4353","authenticated-orcid":false,"given":"Kiana","family":"Rashidi","sequence":"first","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavi P.","family":"Modi","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-6014","authenticated-orcid":false,"given":"Phillip A.","family":"Richmond","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Mangino","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loryn","family":"Byres","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-2494","authenticated-orcid":false,"given":"Cassie","family":"McDonald","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Dalmann","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-3139","authenticated-orcid":false,"given":"Simran","family":"Samra","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L. Del","family":"Bel","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lehman","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7757-8175","authenticated-orcid":false,"given":"Jessica L.","family":"Zambonin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1599-1065","authenticated-orcid":false,"given":"Stuart E.","family":"Turvey","sequence":"additional","affiliation":[{"name":"The Rare Disease Discovery Hub, BC Children's Hospital Research Institute University of British Columbia and British Columbia Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"110","article-title":"Two Sisters Showing Malformations of the Skull and Other Congenital Abnormalities","volume":"1","author":"Carpenter G.","year":"1901","journal-title":"Report of the Society for the Study of Diseases of Children"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280208"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.08.012"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011651"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty191"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac058"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62174"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbs017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.027"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010024\u201001624\u20109"}],"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.70124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70124","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:07:23Z","timestamp":1780304843000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/ajmg.a.70124"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70124","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"assertion":[{"value":"2025-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}