{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:10:26Z","timestamp":1788354626729,"version":"build-2803163510"},"reference-count":22,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010381","name":"European Society for Paediatric Endocrinology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010381","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223187\/Z\/21\/Z"],"award-info":[{"award-number":["223187\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SBF009\\1135"],"award-info":[{"award-number":["SBF009\\1135"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2026,3,16]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    Schaaf-Yang syndrome and Prader-Willi syndrome are imprinting disorders that result from the disruption of paternally expressed genes within the 15q11-q13 region. Both conditions present with overlapping clinical features including developmental delay, hypotonia and endocrine abnormalities. Schaaf-Yang syndrome specifically results from heterozygous variants in the paternally expressed\n                    <jats:italic>MAGEL2<\/jats:italic>\n                    gene. Because these variants are often\n                    <jats:italic>de novo<\/jats:italic>\n                    , determining that the variant is on the paternal allele is essential for a definitive diagnosis. Traditional methods, such as methylation-specific PCR, are labour-intensive, while it is challenging to phase variants separated by distances greater than the fragment length (~600\u2009bp) using short-read sequencing. In this study, we used long-read Oxford Nanopore sequencing to perform trio-assisted phasing of a\n                    <jats:italic>de novo MAGEL2<\/jats:italic>\n                    , p.(Gln638Ter) variant identified in two unrelated probands referred for congenital hyperinsulinism genetic testing. Long reads spanning both the variant and informative parental heterozygous variants confirmed that the variant was on the paternal allele and was therefore pathogenic and causative of Schaaf-Yang syndrome and associated with hyperinsulinism in both individuals. Our findings demonstrate the clinical utility of long-read sequencing for enabling trio-assisted variant phasing in imprinting disorders, particularly when phenotypes are incomplete or overlapping. Our findings further highlight congenital hyperinsulinism as a rare but important feature associated with Schaaf-Yang syndrome.\n                  <\/jats:p>","DOI":"10.1136\/jmg-2025-111282","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:20:31Z","timestamp":1774977631000},"page":"432-435","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Long-read sequencing enables trio-assisted phasing of\n                    <i>de novo<\/i>\n                    variants in the imprinted gene\n                    <i>MAGEL2<\/i>"],"prefix":"10.1136","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-0089","authenticated-orcid":false,"given":"Thomas W","family":"Laver","sequence":"first","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeah","family":"Sangha","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Mallin","sequence":"additional","affiliation":[{"name":"Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Cohen","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology and Diabetes Unit, Ruth Rappaport Children\u2019s Hospital, Haifa, Israel"},{"name":"The Ruth & Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u011fmur","family":"\u00dcnsal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin","family":"Demirbilek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew N","family":"Wakeling","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5094-9148","authenticated-orcid":false,"given":"Jasmin J","family":"Bennett","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne A L","family":"Houghton","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"},{"name":"Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonna M E","family":"M\u00e4nnist\u00f6","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"},{"name":"University of Eastern Finland, Joensuu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Dempster","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Clinical and Biomedical Science, University of Exeter, Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"2026062508352764000_63.7.432.1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24054271","article-title":"Prader-Willi Syndrome and Chromosome 15q11.2 BP1-BP2 Region: A Review","volume":"24","author":"Butler","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026062508352764000_63.7.432.2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40650"},{"key":"2026062508352764000_63.7.432.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108690"},{"key":"2026062508352764000_63.7.432.4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s13023-019-1249-4","article-title":"Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy","volume":"14","author":"Negishi","year":"2019","journal-title":"Orphanet J Rare 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