{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:51:13Z","timestamp":1787010673965,"version":"build-2736575974"},"reference-count":58,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>\n                    We assessed the results of genome sequencing for early-onset dementia. Participants were selected from a memory disorders clinic. Genome sequencing was performed along with\n                    <jats:italic>C9orf72<\/jats:italic>\n                    repeat expansion testing. All returned sequencing results were Sanger-validated. Prior clinical diagnoses included Alzheimer's disease, frontotemporal dementia, and unspecified dementia. The mean age of onset was 54 (41\u201376). Fifty percent of patients had a strong family history, 37.5% had some, and 12.5% had no known family history. Nine of 32 patients (28%) had a variant defined as pathogenic or likely pathogenic (P\/LP) by American College of Medical Genetics and Genomics standards, including variants in\n                    <jats:italic>APP<\/jats:italic>\n                    ,\n                    <jats:italic>C9orf72<\/jats:italic>\n                    ,\n                    <jats:italic>CSF1R<\/jats:italic>\n                    , and\n                    <jats:italic>MAPT<\/jats:italic>\n                    . Nine patients (including three with P\/LP variants) harbored established risk alleles with moderate penetrance (odds ratios of \u223c2\u20135) in\n                    <jats:italic>ABCA7<\/jats:italic>\n                    ,\n                    <jats:italic>AKAP9<\/jats:italic>\n                    ,\n                    <jats:italic>GBA<\/jats:italic>\n                    ,\n                    <jats:italic>PLD3<\/jats:italic>\n                    ,\n                    <jats:italic>SORL1<\/jats:italic>\n                    , and\n                    <jats:italic>TREM2<\/jats:italic>\n                    . All six patients harboring these moderate penetrance variants but not P\/LP variants also had one or two\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 alleles. One patient had two\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b54 alleles with no other established contributors. In total, 16 patients (50%) harbored one or more genetic variants likely to explain symptoms. We identified variants of uncertain significance (VUSs) in\n                    <jats:italic>ABI3<\/jats:italic>\n                    ,\n                    <jats:italic>ADAM10<\/jats:italic>\n                    ,\n                    <jats:italic>ARSA<\/jats:italic>\n                    ,\n                    <jats:italic>GRID2IP<\/jats:italic>\n                    ,\n                    <jats:italic>MME<\/jats:italic>\n                    ,\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    ,\n                    <jats:italic>PLCD1<\/jats:italic>\n                    ,\n                    <jats:italic>PSEN1<\/jats:italic>\n                    ,\n                    <jats:italic>TM2D3<\/jats:italic>\n                    ,\n                    <jats:italic>TNK1<\/jats:italic>\n                    ,\n                    <jats:italic>TTC3<\/jats:italic>\n                    , and\n                    <jats:italic>VPS13C<\/jats:italic>\n                    , also often along with other variants. In summary, genome sequencing for early-onset dementia frequently identified multiple established or possible contributory alleles. These observations add support for an oligogenic model for early-onset dementia.\n                  <\/jats:p>","DOI":"10.1101\/mcs.a003491","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T14:35:24Z","timestamp":1576247724000},"page":"a003491","source":"Crossref","is-referenced-by-count":37,"title":["Genome sequencing for early-onset or atypical dementia: high diagnostic yield and frequent observation of multiple contributory alleles"],"prefix":"10.1101","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-5052","authenticated-orcid":false,"given":"J. 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