title: Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome.
abstract: Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Diane
authors.initials: D
authors.lastname: Beysen
authors.forename: Sarah
authors.initials: S
authors.lastname: De Jaegere
authors.forename: David
authors.initials: D
authors.lastname: Amor
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouchard
authors.forename: Sophie
authors.initials: S
authors.lastname: Christin-Maitre
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
authors.forename: Philippe
authors.initials: P
authors.lastname: Touraine
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Grix
authors.forename: Raoul
authors.initials: R
authors.lastname: Hennekam
authors.forename: Françoise
authors.initials: F
authors.lastname: Meire
authors.forename: Nina
authors.initials: N
authors.lastname: Oyen
authors.forename: Louise C
authors.initials: LC
authors.lastname: Wilson
authors.forename: Dalit
authors.initials: D
authors.lastname: Barel
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.forename: Christian
authors.initials: C
authors.lastname: Decock
authors.forename: Patricia
authors.initials: P
authors.lastname: Delbeke
authors.forename: Regina
authors.initials: R
authors.lastname: Ensenauer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ebinger
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hendriks
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
authors.forename: Rachel
authors.initials: R
authors.lastname: Laframboise
authors.forename: Paul
authors.initials: P
authors.lastname: Laissue
authors.forename: Kathleen
authors.initials: K
authors.lastname: Leppig
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Mowat
authors.forename: Luitgard
authors.initials: L
authors.lastname: Neumann
authors.forename: Astrid
authors.initials: A
authors.lastname: Plomp
authors.forename: Nicole
authors.initials: N
authors.lastname: Van Regemorter
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016569:Blepharophimosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005143:Eyelids / Q000002:abnormalities; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D016368:Frameshift Mutation; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016649:Primary Ovarian Insufficiency / Q000235:genetics; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors