{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:58:54Z","timestamp":1781873934168,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The Triggering Receptor Expressed on Myeloid Cells 2 protein (TREM2) plays a crucial role in various biological processes, including osteoclast differentiation, and disease\u2010associated microglia (DAM) activation to regulate neuroinflammation, and phagocytosis in the brain. Genetic variations in <jats:italic>TREM2<\/jats:italic> are implicated in neurodegenerative disorders, such as Nasu\u2010hakola disease (NHD), characterized by bone lesions, neuropsychiatric disorders, and early\u2010onset dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 3 siblings with suspected NHD. Whole\u2010exome sequencing was conducted on the proband to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants in the two other affected siblings, a healthy sister, and the parents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel homozygous deletion (c.549del; p.(Leu184Serfs*5)) in <jats:italic>TREM2<\/jats:italic>. Our literature review reveals 16 <jats:italic>TREM2<\/jats:italic> mutations causing early\u2010onset dementia and bone lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings, alongside previous research, elucidate the clinical spectrum of TREM2\u2010related diseases, aiding accurate diagnosis and patient care. This knowledge is vital for understanding TREM2\u2010dependent DAM and its involvement in the pathogenesis of neurodevelopmental disorders which can help to develop targeted therapies and improve outcomes for TREM2\u2010affected individuals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2476","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T11:30:01Z","timestamp":1718710201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Homozygous <scp><i>TREM2<\/i><\/scp> c.549del; p.(<scp>Leu184Serfs<\/scp>*5) variant causing Nasu\u2010Hakola disease in three siblings in a consanguineous Iraqi family: Case report and review of literature"],"prefix":"10.1002","volume":"12","author":[{"given":"Naser","family":"Gilani","sequence":"first","affiliation":[{"name":"Department of Biology Gaziantep University  Gaziantep Turkey"},{"name":"Farabi Molecular Laboratory  Irbil Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-2923","authenticated-orcid":false,"given":"Fatemeh","family":"Bitarafan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Oslo University Hospital and University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Ozaslan","sequence":"additional","affiliation":[{"name":"Department of Biology Gaziantep University  Gaziantep Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"\u00c5sheim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Oslo University Hospital and University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morteza","family":"Heidari","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic, Department of Pediatric Neurology, Children's Medical Center, Pediatrics Center 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