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However, when such variants occur pre\u2010zygotically in parental germ cells, the recurrence risk might be higher. Still, the recurrence risk estimates are mainly based on empirical data and the prevalence of germline mosaicism is often unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To establish the prevalence of mosaicism in parents of children with intellectual disability syndromes caused by de novo variants, we performed droplet digital PCR on DNA extracted from blood (43 trios), and sperm (31 fathers).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected low\u2010level mosaicism in sperm\u2010derived DNA but not in blood in the father of a child with Kleefstra syndrome caused by an <jats:italic>EHMT1<\/jats:italic> variant. Additionally, we found a higher level of paternal mosaicism in sperm compared to blood in the father of a child with Gillespie syndrome caused by an <jats:italic>ITPR1<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>By employing droplet digital PCR, we detected paternal germline mosaicism in two intellectual disability syndromes. In both cases, the mosaicism level was higher in sperm than blood, indicating that analysis of blood alone may underestimate germline mosaicism. Therefore, sperm analysis can be clinically useful to establish the recurrence risk for parents and improve genetic counselling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1880","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T08:30:30Z","timestamp":1643963430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Detection of germline mosaicism in fathers of children with intellectual disability syndromes caused by de novo variants"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2416-462X","authenticated-orcid":false,"given":"Sofia","family":"Frisk","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Center for Molecular Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Department of Clinical Genetics Karolinska University Laboratory, Karolinska University Hospital  Stockholm 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