{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:35:19Z","timestamp":1791196519207,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,12,11]],"date-time":"2002-12-11T00:00:00Z","timestamp":1039564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2003,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the forkhead transcription factor gene 2 (<jats:italic>FOXL2<\/jats:italic>) were recently reported to cause blepharophimosis\u2010ptosis\u2010epicanthus inversus syndrome (BPES) types I and II. Evidence was provided that BPES type I (eyelid abnormalities and female infertility) is caused by mutations resulting in a truncated FOXL2 protein. In contrast, mutant FOXL2 proteins, either with inserted aminoacids in the forkhead domain or polyalanine tract, or with novel aminoacids at the carboxyl end, were found in BPES type II, in which fertility is generally normal. We report a 32\u2010year\u2010old female patient with sporadic BPES and a history of menstrual cycle irregularities and periods of secondary amenorrhoea. A heterozygous frameshift mutation (c959\u2010960insG) was found in the <jats:italic>FOXL2<\/jats:italic> gene, resulting in a predicted FOXL2 protein with 212 novel aminoacids in the carboxyl end, suggesting BPES type II despite menstrual irregularities. The clinical presentations of our patient and of three female patients with BPES type II in the report of De Baere et al. [2001: Hum Mol Genet 10:1591\u20131600.] indicate phenotypic overlap between BPES type I and II. These observations do not support a clear\u2010cut prediction of female fertility based on the <jats:italic>FOXL2<\/jats:italic> molecular defect. As a consequence, <jats:italic>FOXL2<\/jats:italic> mutation testing in female patients of child\u2010bearing age with BPES should be handled with caution, and a two\u2010step genetic counseling approach, including an initial pre\u2010test information session, is proposed. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.10024","type":"journal-article","created":{"date-parts":[[2003,2,5]],"date-time":"2003-02-05T01:12:40Z","timestamp":1044407560000},"page":"143-146","source":"Crossref","is-referenced-by-count":27,"title":["<i>FOXL2<\/i>\u2010mutations in blepharophimosis\u2010ptosis\u2014epicanthus inversus syndrome (BPES); challenges for genetic counseling in female patients"],"prefix":"10.1002","volume":"117A","author":[{"given":"Siv","family":"Fokstuen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stylianos E.","family":"Antonarakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Blouin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,12,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/109065701753617499"},{"key":"e_1_2_6_3_1","first-page":"785","article-title":"The genetic testing of children. 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