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FOXL2 ‐mutations in blepharophimosis‐ptosis—epicanthus inversus syndrome (BPES); challenges for genetic counseling in female patients
Author(s) -
Fokstuen Siv,
Antonarakis Stylianos E.,
Blouin JeanLouis
Publication year - 2002
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.10024
Subject(s) - blepharophimosis , frameshift mutation , ptosis , genetic counseling , mutation , infertility , premature ovarian failure , genetics , biology , gene , medicine , endocrinology , pregnancy , surgery
Abstract Mutations in the forkhead transcription factor gene 2 ( FOXL2 ) were recently reported to cause blepharophimosis‐ptosis‐epicanthus 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‐year‐old female patient with sporadic BPES and a history of menstrual cycle irregularities and periods of secondary amenorrhoea. A heterozygous frameshift mutation (c959‐960insG) was found in the FOXL2 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 10:1591–1600.] indicate phenotypic overlap between BPES type I and II. These observations do not support a clear‐cut prediction of female fertility based on the FOXL2 molecular defect. As a consequence, FOXL2 mutation testing in female patients of child‐bearing age with BPES should be handled with caution, and a two‐step genetic counseling approach, including an initial pre‐test information session, is proposed. © 2003 Wiley‐Liss, Inc.