{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:31:20Z","timestamp":1789986680376,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T00:00:00Z","timestamp":1544140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008217","name":"Dronning Louises B\u00f8rnehospitals Forskningsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008217","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004752","name":"State Government of Victoria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004752","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>Rett syndrome is rarely suspected in males because of the X\u2010linked dominant inheritance. In the literature, only six male patients have been reported with methyl\u2010CpG\u2010binding protein 2 (<jats:italic>MECP2<\/jats:italic>) mosaicism. Next\u2010generation sequencing (NGS) methods have enabled better detection of somatic mosaicism compared to conventional Sanger sequencing; however, mosaics can still be difficult to detect. We present clinical and molecular findings in two males mosaic for a pathogenic <jats:italic>MECP2<\/jats:italic> variant. Both have been reexamined using deep sequencing of DNA isolated from four different cell tissues (blood, muscle, fibroblasts and oral mucosa). Deep sequencing of the different tissues revealed that the variants were present in all tissues. In one patient, the molecular diagnosis could only be established by reexamination after a normal whole exome sequencing, and the other case is an example of reverse genetic diagnostics. Rett syndrome should be considered in males with neurodevelopmental delay and stereotypical hand movements. Subsequent to clinical diagnosis males should be investigated with NGS\u2010based technologies of <jats:italic>MECP2<\/jats:italic> with high read depth and a low threshold for variant calls. If the initial analysis on full blood derived DNA fails to confirm the suspicion, we recommend repeating the analysis on another tissue, preferentially fibroblasts to increase the diagnostic yield.<\/jats:p>","DOI":"10.1111\/cge.13473","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T07:24:26Z","timestamp":1542007466000},"page":"403-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mosaic <i>MECP2<\/i> variants in males with classical Rett syndrome features, including stereotypical hand movements"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-0792","authenticated-orcid":false,"given":"Bitten","family":"Sch\u00f6newolf\u2010Greulich","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Center for Rett Syndrome, Rigshospitalet  Copenhagen Denmark"},{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Center for Rett Syndrome, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Dun\u00f8","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine","family":"Jespersgaard","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen 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Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral","family":"Topcu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hacettepe Medical School  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simran","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Murdoch Children's Research Institute University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole J.","family":"Van Bergen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Murdoch Children's Research Institute University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Br\u00f8ndum\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina P.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Murdoch Children's Research Institute University of Melbourne  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina R.","family":"Fagerberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital  Odense 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