{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:29:14Z","timestamp":1778102954090,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations in <jats:italic>FOXL2<\/jats:italic> are known to cause autosomal dominant blepharophimosis\u2010ptosis\u2010epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure. In this study, we report results of mutational screening in a Czech and Slovak patient population with BPES.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Case series.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Thirteen probands of Czech and one proband of Slovak origin with BPES and their available family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sanger sequencing and multiplex ligation\u2010dependent probe amplification in 14 probands with BPES. Targeted mutational screening in first\u2010degree relatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>Genetic characterization and phenotype evaluation in Czech and Slovak individuals with BPES and their family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight different mutations were detected including three novel ones: c.5T&gt;G; p.(Met2Arg), c.197C&gt;A; p.(Ala66Glu) and c.701_702insTGCAGCCGCAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC; p.(Ala222_Ala234dup). In one family, the molecular genetic cause of disease was not identified by the methodology used. In 13 pedigrees, a negative family history suggested a <jats:italic>de novo<\/jats:italic> origin, which could be confirmed by targeted mutational screening in four families. One 62\u2010year\u2010old female with the c.663_692dup30 mutation had an atypical phenotype presenting as moderate ptosis compensated by frontalis muscle contraction, no epicanthus inversus and no premature ovarian failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:italic>de novo<\/jats:italic> mutation rate in <jats:italic>FOXL2<\/jats:italic> is exceptionally high compared with other dominant disorders manifesting with an ocular phenotype. In cases reporting a negative family history, careful examination of both parents is important to exclude mild features of the BPES phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12783","type":"journal-article","created":{"date-parts":[[2016,6,10]],"date-time":"2016-06-10T10:06:06Z","timestamp":1465553166000},"page":"757-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Analysis of <i>FOXL2<\/i> detects three novel mutations and an atypical phenotype of blepharophimosis\u2010ptosis\u2010epicanthus inversus syndrome"],"prefix":"10.1111","volume":"44","author":[{"given":"Anna","family":"Krepelova","sequence":"first","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University in Prague and University Hospital Motol  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Simandlova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University in Prague and University Hospital Motol  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marketa","family":"Vlckova","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine Charles University in Prague and University Hospital Motol  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Kuthan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea L","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences University of Auckland  Auckland New Zealand"},{"name":"Eye Department, Greenlane Clinical Centre Auckland District Health Board  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-8486","authenticated-orcid":false,"given":"Petra","family":"Liskova","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague  Prague Czech Republic"},{"name":"Institute of Inherited Metabolic Disorders, First Faculty of Medicine Charles University in Prague and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"653","article-title":"Premature ovarian failure and forkhead transcription factor FOXL2: blepharophimosis\u2010ptosis\u2010epicanthus inversus syndrome and ovarian dysfunction","volume":"2","author":"De Baere E","year":"2005","journal-title":"Pediatr Endocrinol 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