title: BPES with atypical premature ovarian insufficiency, and evidence of mitotic recombination, in a woman with trisomy X and a translocation t(3;11)(q22.3;q14.1).
abstract: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder characterized by a complex dysgenesis of the eyelids and premature ovarian insufficiency. FOXL2 located at 3q22.3, encoding a forkhead transcription factor, is the only gene known to be responsible for BPES. We describe a patient diagnosed with BPES with atypical ovarian failure, characterized by normal levels of gonadotropins, who was found to have trisomy X as well as a translocation (3;11)(q22.3;q14.1). The translocation breakpoint at 3q22.3 is located upstream of the FOXL2 gene and most likely causes BPES by separating the FOXL2 transcription unit from its cis-regulatory sequences. By array analysis we detected mosaicism for the balanced and an unbalanced form of the translocation in blood cells. We propose mitotic recombination as the likely mechanism of the mosaicism formation. Mitotic recombination is a common phenomenon in human cells. Thus, we hypothesize that it may be one of the mechanisms responsible for cryptic imbalances and possible abnormal phenotypes in some carriers of balanced rearrangements.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Children's & Women's Hospital, Vancouver, BC, Canada. ksbartusiak@cw.bc.ca
authors.forename: Kamilla
authors.initials: K
authors.lastname: Schlade-Bartusiak
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
authors.forename: Brenda
authors.initials: B
authors.lastname: Lomax
authors.forename: Hélène
authors.initials: H
authors.lastname: Bruyère
authors.forename: Tanya
authors.initials: T
authors.lastname: Gillan
authors.forename: Sara
authors.initials: S
authors.lastname: Hamilton
authors.forename: Barbara
authors.initials: B
authors.lastname: McGillivray
authors.forename: Patrice
authors.initials: P
authors.lastname: Eydoux
mesh_terms: D000328:Adult; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008938:Mitosis; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000378:metabolism*; D011995:Recombination, Genetic; D012729:Sex Chromosome Aberrations; D058533:Sex Chromosome Disorders of Sex Development / Q000235:genetics*; D014178:Translocation, Genetic; D014314:Trisomy / Q000235:genetics*