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For a long time, loss\u2010of\u2010function (LoF) mutations in <jats:italic><jats:styled-content style=\"fixed-case\">SMC1A<\/jats:styled-content><\/jats:italic> were considered incompatible with life, as such mutations had not been reported in neither male nor female patients. However, recently, the authors and others reported LoF mutations in females with intellectual disability (<jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>) and epilepsy.<\/jats:p><jats:p>Here we present the detailed phenotype of two females with <jats:italic>de novo<\/jats:italic> LoF mutations in <jats:italic><jats:styled-content style=\"fixed-case\">SMC1A<\/jats:styled-content><\/jats:italic>, including a <jats:italic>de novo<\/jats:italic> mutation of single base deletion [c.2364del, p.(<jats:styled-content style=\"fixed-case\">Asn788Lysfs<\/jats:styled-content>*10)], predicted to result in a frameshift, and a <jats:italic>de novo<\/jats:italic> deletion of exon 16, resulting in an out\u2010of\u2010frame <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> splice product [p.(<jats:styled-content style=\"fixed-case\">Leu808Argfs<\/jats:styled-content>*6)]. By combining our patients with the other recently reported females carrying <jats:italic><jats:styled-content style=\"fixed-case\">SMC1A<\/jats:styled-content><\/jats:italic> LoF mutations, we ascertained a phenotypic spectrum of (severe) <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>, therapy\u2010resistant epilepsy, absence\/delay of speech, hypotonia and small hands and feet. Our data show the existence of a novel phenotypic entity \u2013 <jats:italic>distinct from <jats:styled-content style=\"fixed-case\">CdLS<\/jats:styled-content><\/jats:italic> \u2013 and caused by <jats:italic>de novo <jats:styled-content style=\"fixed-case\">SMC1A<\/jats:styled-content><\/jats:italic> LoF mutations.<\/jats:p>","DOI":"10.1111\/cge.12729","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T08:13:18Z","timestamp":1452499998000},"page":"413-419","source":"Crossref","is-referenced-by-count":40,"title":["<i>De novo<\/i> loss\u2010of\u2010function mutations in X\u2010linked <i><scp>SMC1A<\/scp><\/i> cause severe <scp>ID<\/scp> and therapy\u2010resistant epilepsy in females: expanding the phenotypic spectrum"],"prefix":"10.1111","volume":"90","author":[{"given":"S.","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kleefstra","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.H.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Pfundt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.Y.","family":"Hehir\u2010Kwa","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Gilissen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.A.","family":"Veltman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Donders Centre for Neuroscience Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Department of Clinical Genetics Maastricht University Medical Centre  Maastricht the 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