{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:39:30Z","timestamp":1786639170254,"version":"build-2736575974"},"reference-count":21,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"abstract":"<jats:p>Introduction: Dual molecular diagnoses are increasingly recognized with expanded genomic testing, and may result in blended phenotypes when two independent pathogenic findings contribute to the clinical presentation. Case Presentation: A 3-year-old female patient presented with seizures beginning at 8 months of age (generalized tonic-clonic), severe global developmental delay\/intellectual disability, generalized hypotonia, absent meaningful speech, and microcephaly (head circumference 44.1 cm, &lt;3rd percentile). Craniofacial features included midface retrusion\/hypoplasia, thick eyebrows, bilateral epicanthal folds, upslanting palpebral fissures, large ears, a wide mouth, a full lower lip, and a low posterior hairline. Electroencephalography showed age-inappropriate background activity with frequent high-amplitude bifrontal spike-slow wave discharges that often generalized and occasionally displayed a hypsarrhythmia-like pattern. Cranial magnetic resonance imaging was reported as showing a mega cisterna magna variation. Conclusion: Exome sequencing (ES) identified a heterozygous missense variant in HECW2, NM_001348768.2:c.4485G&gt;T p.(Arg1495Ser). Copy-number variant (CNV) analysis of the ES data detected an approximately 2.6 megabase (Mb) heterozygous deletion on chromosome 15, subsequently confirmed by chromosomal microarray analysis as a 2.79 Mb 15q25.2\u2013q25.3 deletion and classified as pathogenic according to American College of Medical Genetics and Genomics\/Clinical Genome Resource (ACMG\/ClinGen) technical standards. Both alterations were de novo. This case represents a rare dual molecular diagnosis involving a HECW2 missense variant and a 15q25.2-q25.3 deletion, supporting a potential blended phenotype and expanding the molecular and phenotypic spectrum of HECW2-related neurodevelopmental disorder.<\/jats:p>","DOI":"10.1159\/000553561","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:01:14Z","timestamp":1783958474000},"page":"1-7","source":"Crossref","is-referenced-by-count":0,"title":["A HECW2 Missense Variant with a Coexisting 15q25.2-q25.3 Deletion: A Dual Molecular Diagnosis Case Report"],"prefix":"10.1159","author":[{"given":"Javid","family":"Taghiyev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-9279","authenticated-orcid":false,"given":"Alper","family":"Gezdirici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-4768","authenticated-orcid":false,"given":"Tuna Eren","family":"Esen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000001072"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201899"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1159\/000438812"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516767"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306555"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.142"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-291x(03)01347-0"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103814"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103943"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.03.005"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1159\/000545680"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62363"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107871"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2020.180"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35695"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36203"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3092"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.4103\/jmu.jmu_78_22"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14880"}],"container-title":["Molecular Syndromology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000553561","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:08:05Z","timestamp":1786637285000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000553561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":21,"URL":"https:\/\/doi.org\/10.1159\/000553561","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.32963012","asserted-by":"subject"}]},"ISSN":["1661-8769","1661-8777"],"issn-type":[{"value":"1661-8769","type":"print"},{"value":"1661-8777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]}}}