{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T17:41:48Z","timestamp":1767634908630,"version":"3.48.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C17183\/A23303"],"award-info":[{"award-number":["C17183\/A23303"]}],"id":[{"id":"10.13039\/501100000289","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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Currently, exome and genome sequencing achieve a diagnostic rate of 30%\u201350% for rare genetic diseases. With multi\u2010modal technologies profiling the genome, transcriptome, and epigenome, interrogation of genomic elements outside of protein\u2010coding regions shows potential to improve this as demonstrated herein. Siblings with sensorineural hearing loss, microcephaly, intellectual impairment, and growth restriction were seen in consultation. Following extensive clinical testing, long\u2010read whole genome and cDNA\u2010based transcriptome sequencing on the Oxford Nanopore platform identified a homozygous 1.6\u2009kb deletion of the 5\u2032 UTR and promoter region of\n                    <jats:italic>DDX11<\/jats:italic>\n                    , a gene associated with Warsaw breakage syndrome. The deletion included the hypomethylated CpG island regulating\n                    <jats:italic>DDX11<\/jats:italic>\n                    , led to a loss of expression of DDX11 mRNA and protein, and resulted in the characteristic \u201crailroad chromosome.\u201d Identifying a causal variant for this family required expanding the search space for genomic variants beyond protein\u2010coding regions, and multi\u2010modal data integration enabled a more holistic approach to variant prioritization and classification prior to pursuing targeted protein and functional assays. This multi\u2010modal genome\u2010wide approach heralds promise for patients on the diagnostic odyssey and who have exhausted standard of care testing.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64252","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T10:20:15Z","timestamp":1757672415000},"page":"432-437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Non\u2010Coding Causative Variant Underlying Warsaw Breakage Syndrome Using Long\u2010Read Based Genomic Sequencing and Transcriptome Analysis"],"prefix":"10.1002","volume":"200","author":[{"given":"Makenna","family":"DuBois","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Dixon","sequence":"additional","affiliation":[{"name":"Alamya Health, PBC  Clever Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Sherlaw\u2010Sturrock","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences University of Birmingham  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoqing","family":"Shen","sequence":"additional","affiliation":[{"name":"Alamya Health, PBC  Clever Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Probst","sequence":"additional","affiliation":[{"name":"Alamya Health, PBC  Clever Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorne","family":"Clarke","sequence":"additional","affiliation":[{"name":"Alamya Health, PBC  Clever Missouri 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UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1882-6014","authenticated-orcid":false,"given":"Phillip","family":"Richmond","sequence":"additional","affiliation":[{"name":"Alamya Health, PBC  Clever Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California  Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01270-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40482"},{"issue":"3","key":"e_1_2_9_4_1","first-page":"111","article-title":"Warsaw Breakage Syndrome: An Etiology for Congenital Microcephaly and Sensorineural 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