{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:46:44Z","timestamp":1790761604901,"version":"4.1.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genomic mosaicism in parental gametes and peripheral tissues is an important consideration for genetic counseling. We studied a Chinese cohort affected by a severe epileptic disorder, Dravet syndrome (DS). There were 56 fathers who donated semen and 15 parents who donated multiple peripheral tissue samples. We used an ultra-sensitive quantification method, micro-droplet digital PCR (mDDPCR), to detect parental mosaicism of the proband\u2019s pathogenic mutation in <jats:italic>SCN1A<\/jats:italic>, the causal gene of DS in 112 families. Ten of the 56 paternal sperm samples were found to exhibit mosaicism of the proband\u2019s mutations, with mutant allelic fractions (MAFs) ranging from 0.03% to 39.04%. MAFs in the mosaic fathers\u2019 sperm were significantly higher than those in their blood (<jats:italic>p<\/jats:italic>\u2009=\u20090.00098), even after conditional probability correction (<jats:italic>p\u2019<\/jats:italic>\u2009=\u20090.033). In three mosaic fathers, ultra-low fractions of mosaicism (MAF\u2009&lt;\u20091%) were detected in the sperm samples. In 44 of 45 cases, mosaicism was also observed in other parental peripheral tissues. Hierarchical clustering showed that MAFs measured in the paternal sperm, hair follicles and urine samples were clustered closest together. Milder epileptic phenotypes were more likely to be observed in mosaic parents (<jats:italic>p<\/jats:italic>\u2009=\u20093.006e-06). Our study provides new insights for genetic counseling.<\/jats:p>","DOI":"10.1038\/s41598-017-15814-7","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T16:07:22Z","timestamp":1510243642000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-0023","authenticated-orcid":false,"given":"Xiaoxu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam Yongxin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"August Yue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiru","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"15814_CR1","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/nrg906","volume":"3","author":"H Youssoufian","year":"2002","unstructured":"Youssoufian, H. & Pyeritz, R. E. Mechanisms and consequences of somatic mosaicism in humans. Nature reviews. Genetics \n                           3, 748\u2013758, https:\/\/doi.org\/10.1038\/nrg906 (2002).","journal-title":"Nature reviews. Genetics"},{"key":"15814_CR2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nrg3241","volume":"13","author":"JA Veltman","year":"2012","unstructured":"Veltman, J. A. & Brunner, H. G. De novo mutations in human genetic disease. Nature reviews. Genetics \n                           13, 565\u2013575, https:\/\/doi.org\/10.1038\/nrg3241 (2012).","journal-title":"Nature reviews. Genetics"},{"key":"15814_CR3","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nrg3424","volume":"14","author":"LG Biesecker","year":"2013","unstructured":"Biesecker, L. G. & Spinner, N. B. A genomic view of mosaicism and human disease. Nature reviews. 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