Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

• DOI: 10.1007/s00439-021-02268-1
• Publication Date: 2021-03-12T08:02:26Z
• Authors: Irma Järvelä; Tuomo Määttä; Anushree Acharya; Juha Leppälä; Shalini N. Jhangiani; Maria Arvio; Auli Siren; Minna Kankuri-Tam...; Hannaleena Kokkonen; Maarit Palomäki; Teppo Varilo; Mary Fang; Trevor D. Hadley; Angad Jolly; Tarja Linnankivi; Ritva Paetau; Anni Saarela; Reetta Kälviäinen; Jan Olme; Liz M. Nouel-Saied; Diana M. Cornejo-...; Lorida Llaci; James R. Lupski; Jennifer E. Posey; Suzanne M. Leal; Isabelle Schrauwen
• Keywords: Founder effect; Human genetics; Exome; Candidate gene

Abstract The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be interest to study (ID) and the contribution ARID. Here, we used a genotype-driven approach genetic landscape ID population Finland. A total 39 families with syndromic non-syndromic were analyzed using exome sequencing, which revealed variant known gene 27 families. Notably, 75% these variants genes de novo or suspected (64% dominant; 11% X-linked) 25% inherited (14% recessive; 7% X-linked; 4% dominant). dual molecular diagnosis was suggested two (5%). Via additional analysis testing, identified three cases an abnormal karyotype, including chr21q22.12q22.2 uniparental disomy mosaic interstitial 2.7 Mb deletion covering DYRK1A KCNJ6. Overall, pathogenic likely 64% (25/39) Last, report alternate inheritance model for 3 ( UBA7 , DDX47 DHX58 ) discuss potential candidate ID, SYPL1 ERGIC3 homozygous POLR2F DNAH3. In summary, similar other European populations, most common underlying Finnish population, limited ARID etiology, though driven by variation latter case.