title: Identification of novel mutations in FOXL2 associated with premature ovarian failure.
abstract: Premature ovarian failure (POF) affects approximately 1% of women and is known to be caused by sex chromosome abnormalities, iatrogenic agents and autoimmune diseases, but in the majority of cases the cause is unknown. However, several families have been identified as having an inherited predisposition to POF, suggesting a genetic component to the condition in these cases. The FOXL2 gene of 70 POF patients from New Zealand and Slovenia was screened for mutations. In a Slovenian POF patient, a novel 30 bp deletion was identified that was predicted to remove 10 out of 14 alanines (A221_A230del), from the polyalanine tract downstream of the winged helix/forkhead domain of the FOXL2 protein. A novel single nucleotide substitution, 772(1009)T>A, which is predicted to change amino acid 258 from tyrosine to asparagine (Y258N), was identified in a New Zealand POF patient. Neither mutation was identified in 200 normal control chromosomes from 100 control samples. Three previously unreported single nucleotide substitutions, considered to be non-functional polymorphisms, were also identified.
authors.affiliation: Department of Obstetrics and Gynaecology, National Women's Hospital, Auckland, Finland.
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.forename: A L
authors.initials: AL
authors.lastname: Chand
authors.forename: I M
authors.initials: IM
authors.lastname: Winship
authors.forename: K
authors.initials: K
authors.lastname: Gersak
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: A N
authors.initials: AN
authors.lastname: Shelling
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009520:New Zealand; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion; D017524:Slovenia; 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