{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:21:49Z","timestamp":1787898109865,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1122387"],"award-info":[{"award-number":["APP1122387"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020111","name":"Therapeutic Innovation Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020111","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001793","name":"Queensland University of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cerebral small vessel disease (CSVD) describes a range of neurological diseases affecting the small arteries, veins, and capillaries which supply the white matter and deep grey matter structures of the brain. They are the most common form of cerebrovascular disease, accounting for almost half of vascular dementia cases and approximately 20% of stroke incidence globally. Genetic testing is a routine diagnostic tool for monogenic CSVDs; however, less than 20% of patients have a causal variant in a known gene. Genetic testing for these disorders focuses on single nucleotide variants and short insertions or deletions, with larger genomic variation often unexplored as a cause of disease. In this study we performed whole\u2010exome sequencing (WES) on 111 patients suspected of familial CSVD that had previously tested negative for pathogenic variants in seven known CSVD genes (\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    ,\n                    <jats:italic>HTRA1<\/jats:italic>\n                    ,\n                    <jats:italic>COL4A1<\/jats:italic>\n                    ,\n                    <jats:italic>COL4A2<\/jats:italic>\n                    ,\n                    <jats:italic>TREX1<\/jats:italic>\n                    ,\n                    <jats:italic>GLA<\/jats:italic>\n                    , and\n                    <jats:italic>FOXC1)<\/jats:italic>\n                    . Bioinformatic analysis of WES data, multiplex ligation\u2010dependent probe amplification, quantitative real\u2010time polymerase chain reaction assays, and Nanopore long\u2010read sequencing were used to identify suspected copy number variants. This work identified four candidate CNVs across\n                    <jats:italic>NOTCH3<\/jats:italic>\n                    ,\n                    <jats:italic>LMNB1<\/jats:italic>\n                    , and\n                    <jats:italic>COL4A2<\/jats:italic>\n                    which are potential causes of CSVD and highlights the need for further investigation of more complex forms of genetic variation and their potential roles as causal of CSVD.\n                  <\/jats:p>","DOI":"10.1111\/cge.70233","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:12:01Z","timestamp":1787897521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Copy Number Variants as a Suspected Cause of Cerebral Small Vessel Disease"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3779-6160","authenticated-orcid":false,"given":"Solomon K.","family":"Guyler","sequence":"first","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-4333","authenticated-orcid":false,"given":"Neven","family":"Maksemous","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"},{"name":"Central Analytical Research Facility (CARF) Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-5862","authenticated-orcid":false,"given":"Rodney A.","family":"Lea","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"},{"name":"Central Analytical Research Facility (CARF) Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8512-1498","authenticated-orcid":false,"given":"Heidi G.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5475","authenticated-orcid":false,"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences Queensland University of Technology (QUT)  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"e20190218","DOI":"10.1590\/1678-4685-gmb-2019-0218","article-title":"Copy Number Variation (CNV) Identification, Interpretation, and Database From Brazilian Patients","volume":"43","author":"Godoy V.","year":"2020","journal-title":"Genetics and Molecular Biology"},{"issue":"4","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s40142-017-0129-2","article-title":"Copy Number Variation Disorders","volume":"5","author":"Shaikh T. H.","year":"2017","journal-title":"Current Genetic Medicine Reports"},{"issue":"3","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrg3871","article-title":"A Copy Number Variation Map of the Human Genome","volume":"16","author":"Zarrei M.","year":"2015","journal-title":"Nature Reviews. Genetics"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.gde.2021.05.002","article-title":"Editorial Overview: Rare CNV Disorders and Neuropsychiatric Phenotypes: Opportunities, Challenges, Solutions","volume":"68","author":"Mulle J. 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K.","year":"2021","journal-title":"Journal of Neurology"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2024.105297","article-title":"Clinical and Neuroradiological Spectrum of Biallelic Variants in NOTCH3","volume":"107","author":"Iruzubieta P.","year":"2024","journal-title":"eBioMedicine"},{"issue":"6","key":"e_1_2_11_27_1","doi-asserted-by":"crossref","DOI":"10.1212\/NXG.0000000000000292","article-title":"Duplication and Deletion Upstream of LMNB1 in Autosomal Dominant Adult\u2010Onset Leukodystrophy","volume":"4","author":"Mezaki N.","year":"2018","journal-title":"Neurology Genetics"},{"key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.sbi.2020.06.017","article-title":"Structure and Unique Mechanical Aspects of Nuclear Lamin Filaments","volume":"64","author":"Tenga R.","year":"2020","journal-title":"Current Opinion in Structural Biology"},{"issue":"1","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-11684-x","article-title":"Structural Basis for Lamin Assembly at the Molecular Level","volume":"10","author":"Ahn J.","year":"2019","journal-title":"Nature Communications"},{"issue":"4","key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ajhg.2020.08.015","article-title":"De Novo Variants in LMNB1 Cause Pronounced Syndromic Microcephaly and Disruption of Nuclear Envelope Integrity","volume":"107","author":"Cristofoli F.","year":"2020","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2023.1263310","article-title":"Lamin B1 as a Key Modulator of the Developing and Aging Brain","volume":"17","author":"Koufi F. 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