{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:38:37Z","timestamp":1787312317825,"version":"build-2736575974"},"reference-count":54,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:p>Background: Homozygous variants of the TREM2 and TYROBP genes have been shown to be causative for multiple bone cysts and neurodegeneration leading to progressive dementia (NHD, Nasu-Hakola disease). Objective: To determine if biallelic variants of these genes and\/or oligogenic inheritance could be responsible for a wider spectrum of neurodegenerative conditions. Methods: We analyzed 52 genes associated with neurodegenerative disorders using targeted next generation sequencing in a selected group of 29 patients (n\u200a=\u200a14 Alzheimer\u2019s disease, n\u200a=\u200a8 frontotemporal dementia, n\u200a=\u200a7 amyotrophic lateral sclerosis) carrying diverse already determined rare variants in exon 2 of TREM2. Molecular modeling was used to get an insight into the potential effects of the mutation. Results: We identified a novel mutation c.401_406delinsTCTAT; p.(Asp134Valfs*55) in exon 3 of TREM2 in an Alzheimer\u2019s disease patient also carrying the p.Arg62His TREM2 variant. Molecular modeling revealed that the identified mutation prevents anchoring of the TREM2 protein in the membrane, leaving the core of the Ig-like domain intact. Conclusion: Our results expand the spectrum of neurodegenerative diseases, where the carriers of biallelic mutations in TREM2 have been described for Alzheimer\u2019s disease, and highlight the impact of variant burden in other genes on phenotypic heterogeneity.<\/jats:p>","DOI":"10.3233\/jad-220210","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T11:26:47Z","timestamp":1661254007000},"page":"1211-1219","source":"Crossref","is-referenced-by-count":1,"title":["TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders"],"prefix":"10.1177","volume":"89","author":[{"given":"Mariusz","family":"Berdy\u0144ski","sequence":"first","affiliation":[{"name":"Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Ludwiczak","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Bioinformatics, Centre of New Technologies, University of Warsaw, Warsaw, Poland"},{"name":"Laboratory of Bioinformatics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Barczak","sequence":"additional","affiliation":[{"name":"Rare and Civilisation Diseases Research Platform, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Barcikowska-Kotowicz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Ku\u017ama-Kozakiewicz","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland"},{"name":"Department of Neurology, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanis\u0142aw","family":"Dunin-Horkawicz","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Bioinformatics, Centre of New Technologies, University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezary","family":"\u017bekanowski","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Borzemska","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, 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