title: A new heterozygous mutation of the FOXL2 gene is associated with a large ovarian cyst and ovarian dysfunction in an adolescent girl with blepharophimosis/ptosis/epicanthus inversus syndrome.
abstract: Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of her FOXL2 gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that the FOXL2 mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to known FOXL2 mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.
authors.affiliation: Hospital for Children and Adolescents and. klemens.raile@medizin.uni-leipzig.de
authors.forename: K
authors.initials: K
authors.lastname: Raile
authors.forename: H
authors.initials: H
authors.lastname: Stobbe
authors.forename: R B
authors.initials: RB
authors.lastname: Tröbs
authors.forename: W
authors.initials: W
authors.lastname: Kiess
authors.forename: R
authors.initials: R
authors.lastname: Pfäffle
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D016569:Blepharophimosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008969:Molecular Sequence Data; D009154:Mutation; D010048:Ovarian Cysts / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone