{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:39:31Z","timestamp":1792985971156,"version":"4.5.0"},"reference-count":26,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    Nasu\u2013Hakola disease is a rare autosomal recessive disorder characterized by progressive cognitive decline and bone cyst formation and is commonly associated with triggering receptor expressed on myeloid cells 2 (\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    ) variants. Herein, we report a novel\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    frameshift variant in a middle-aged man from a consanguineous Chinese family who presented with early-onset dementia and right ankle pain. Neuroimaging and skeletal examinations revealed cerebral atrophy and bone cystic lesions. Whole-exome sequencing followed by Sanger confirmation identified a homozygous\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    c.257del (p.D86Afs*103) variant. The patient was diagnosed with Nasu\u2013Hakola disease, and his cognitive deterioration continued despite treatment with donepezil and memantine. Functional assays in human embryonic kidney 293T cells demonstrated preserved mRNA expression of the mutant construct but markedly reduced protein levels compared with that of wild-type. We also conducted a descriptive literature review of 54 previously reported cases of homozygous or compound heterozygous\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    variants to highlight the variability in neurodegenerative and skeletal phenotypes. To the best of our knowledge, this is the first report of a\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    c.257del variant in a Chinese family. Our findings expand the mutational spectrum of Nasu\u2013Hakola disease and highlight substantial phenotypic heterogeneity, emphasizing the importance of early genetic testing in patients with unexplained early-onset dementia, even in the absence of bone lesions.\n                  <\/jats:p>","DOI":"10.1177\/03000605261456056","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:24:35Z","timestamp":1781832275000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel homozygous\n                    <i>TREM2<\/i>\n                    c.257del variant in a Chinese family with Nasu\u2013Hakola disease: A case study and literature review"],"prefix":"10.1177","volume":"54","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, China"},{"name":"Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation, Zhejiang University School of Medicine, China"},{"name":"State Key Laboratory of Transvascular Implantation Devices, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Rong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Rong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, China"},{"name":"Department of Neurology, Shaoxing People\u2019s Hospital, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation, Zhejiang University School of Medicine, China"},{"name":"Department of Medical Genetics and Center for Rare Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-7297","authenticated-orcid":false,"given":"Hong-Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, China"},{"name":"Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation, Zhejiang University School of Medicine, China"},{"name":"State Key Laboratory of Transvascular Implantation Devices, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_3_10_2_2","first-page":"89","article-title":"The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective","volume":"5","author":"Xing J","year":"2015","unstructured":"Xing J, Titus AR, Humphrey MB. The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. Res Rep Biochem 2015; 5: 89\u2013100.","journal-title":"Res Rep Biochem"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.03.008"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.12.009"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.9.753"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12246"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004747"},{"key":"e_1_3_10_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.579"},{"key":"e_1_3_10_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000160304.00003.CA"},{"key":"e_1_3_10_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.6.825-a"},{"key":"e_1_3_10_12_2","first-page":"98","article-title":". Nasu-Hakola disease: a rare cause of dementia and cystic bone lesions, report of a new Turkish family","volume":"55","author":"Koseoglu E","year":"2018","unstructured":"Koseoglu E, Tepge\u00e7 F, Yetkin MF, et\u00a0al . Nasu-Hakola disease: a rare cause of dementia and cystic bone lesions, report of a new Turkish family. Noro Psikiyatr Ars 2018; 55: 98\u2013102.","journal-title":"Noro Psikiyatr Ars"},{"key":"e_1_3_10_13_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201085"},{"key":"e_1_3_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.05.1751"},{"key":"e_1_3_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.003"},{"key":"e_1_3_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.06.005"},{"key":"e_1_3_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.02.016"},{"key":"e_1_3_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.04.010"},{"key":"e_1_3_10_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.01.009"},{"key":"e_1_3_10_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03311.x"},{"key":"e_1_3_10_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/342259"},{"key":"e_1_3_10_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1491"},{"key":"e_1_3_10_23_2","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2024.140568"},{"key":"e_1_3_10_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2476"},{"key":"e_1_3_10_25_2","first-page":"e98664","article-title":"Nasu-Hakola disease presenting as rapidly progressive dementia with seizures: a TREM2 mutation case without skeletal involvement","volume":"17","author":"Sarkar Z","year":"2025","unstructured":"Sarkar Z, Alam MM, Chaudhari A. Nasu-Hakola disease presenting as rapidly progressive dementia with seizures: a TREM2 mutation case without skeletal involvement. Cureus J. Med Science 2025; 17: e98664.","journal-title":"Cureus J. Med Science"},{"key":"e_1_3_10_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000547"},{"key":"e_1_3_10_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-023-05770-7"}],"container-title":["Journal of International Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605261456056","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03000605261456056","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03000605261456056","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T22:04:07Z","timestamp":1782079447000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03000605261456056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1177\/03000605261456056"],"URL":"https:\/\/doi.org\/10.1177\/03000605261456056","relation":{},"ISSN":["0300-0605","1473-2300"],"issn-type":[{"value":"0300-0605","type":"print"},{"value":"1473-2300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"03000605261456056"}}