{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:44:54Z","timestamp":1778658294487,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003748","name":"Svenska S\u00e4llskapet f\u00f6r Medicinsk Forskning","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005423","name":"Akademiska Sjukhuset","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>De novo<\/jats:italic> mutations contribute significantly to severe early\u2010onset genetic disorders. Even if the mutation is apparently <jats:italic>de novo<\/jats:italic>, there is a recurrence risk due to parental germ line mosaicism, depending on in which gonadal generation the mutation occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We demonstrate the power of using SMRT sequencing and ddPCR to determine parental origin and allele frequencies of <jats:italic>de novo<\/jats:italic> mutations in germ cells in two families whom had undergone assisted reproduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the first family, a <jats:italic>TCOF1<\/jats:italic> variant c.3156C&gt;T was identified in the proband with Treacher Collins syndrome. The variant affects splicing and was determined to be of paternal origin. It was present in &lt;1% of the paternal germ cells, suggesting a very low recurrence risk. In the second family, the couple had undergone several unsuccessful pregnancies where a <jats:italic>de novo<\/jats:italic> mutation <jats:italic>PTPN11<\/jats:italic> c.923A&gt;C causing Noonan syndrome was identified. The variant was present in 40% of the paternal germ cells suggesting a high recurrence risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings highlight a successful strategy to identify the parental origin of mutations and to investigate the recurrence risk in couples that have undergone assisted reproduction with an unknown donor or in couples with gonadal mosaicism that will undergo preimplantation genetic diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.5156","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T14:13:13Z","timestamp":1505743993000},"page":"1146-1154","source":"Crossref","is-referenced-by-count":23,"title":["A novel approach using long\u2010read sequencing and ddPCR to investigate gonadal mosaicism and estimate recurrence risk in two families with developmental disorders"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3000-0696","authenticated-orcid":false,"given":"Maria","family":"Wilbe","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2332-074X","authenticated-orcid":false,"given":"Sanna","family":"Gudmundsson","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josefin","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Ameur","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva\u2010Lena","family":"Stattin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"Anner\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Malmgren","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institute  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Frykholm","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Louise","family":"Bondeson","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics, and Pathology, Science for Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3241"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.145"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3424"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12156"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq231"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.29"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20159"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/ng0296-130","article-title":"Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. 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