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Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7\u00a0Mb deletion covering\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    and\n                    <jats:italic>KCNJ6.<\/jats:italic>\n                    Overall, a pathogenic or likely pathogenic variant was identified in 64% (25\/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (\n                    <jats:italic>UBA7<\/jats:italic>\n                    ,\n                    <jats:italic>DDX47<\/jats:italic>\n                    ,\n                    <jats:italic>DHX58<\/jats:italic>\n                    ) and discuss potential candidate genes for ID, including\n                    <jats:italic>SYPL1<\/jats:italic>\n                    and\n                    <jats:italic>ERGIC3<\/jats:italic>\n                    with homozygous founder variants and de novo variants in\n                    <jats:italic>POLR2F<\/jats:italic>\n                    and\n                    <jats:italic>DNAH3.<\/jats:italic>\n                    In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.\n                  <\/jats:p>","DOI":"10.1007\/s00439-021-02268-1","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T03:02:26Z","timestamp":1615518146000},"page":"1011-1029","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of 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Am J Med Genet 155:113\u2013119. https:\/\/doi.org\/10.1002\/ajmg.a.33735","journal-title":"Am J Med Genet"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-021-02268-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00439-021-02268-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-021-02268-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T04:04:04Z","timestamp":1623470644000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00439-021-02268-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,12]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["2268"],"URL":"https:\/\/doi.org\/10.1007\/s00439-021-02268-1","relation":{},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,12]]},"assertion":[{"value":"12 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The material is original research and has not been previously published or submitted to any other journal. J.R.L. has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing conducted at Baylor Genetics (BG) Laboratories. Other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Bioinformatic analyses were done with publicly available software packages as described in the methods. Custom codes to aid in variant filtering are available upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability\u00a0(software application or custom code)"}},{"value":"The parents or legal guardians of all patients and their healthy siblings in this study provided written informed consent to participate in the study. The study was approved by the ethics committees of the Hospital District of Helsinki and Uusimaa (# HUS\/2532\/2017) and the Institutional Review Boards of Columbia University (IRB-AAAS3433) and Baylor College of Medicine (protocol H-29697).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The parents or legal guardians of all patients and their healthy siblings in this study provided written consent to publish the results of this study. A separate written informed consent was obtained from the parents or legal guardians to publish the photos of the patients. The study was approved by the ethics committees of the Hospital District of Helsinki and Uusimaa (# HUS\/2532\/2017) and the Institutional Review Boards of Columbia University (IRB-AAAS3433) and Baylor College of Medicine (protocol H-29697).","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The following databases and web resources were used for this study:\nCADD,\n                      \n                      ,\n                      \n                      ,\n                      \n                      Ensembl,\n                      \n                      GATK,\n                      \n                      gnomAD browser,\n                      \n                      MutationTaster,\n                      \n                      OMIM,\n                      \n                      PolyPhen-2,\n                      \n                      SIFT,\n                      \n                      SMART,\n                      \n                      UCSC browser,\n                      \n                      UniProt,\n                      \n                      .","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Databases and web resources"}}]}}