Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome.
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.
Beysen
Diane
D
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
De Jaegere
Sarah
S
Amor
David
D
Bouchard
Philippe
P
Christin-Maitre
Sophie
S
Fellous
Marc
M
Touraine
Philippe
P
Grix
Arthur W
AW
Hennekam
Raoul
R
Meire
Françoise
F
Oyen
Nina
N
Wilson
Louise C
LC
Barel
Dalit
D
Clayton-Smith
Jill
J
de Ravel
Thomy
T
Decock
Christian
C
Delbeke
Patricia
P
Ensenauer
Regina
R
Ebinger
Friedrich
F
Gillessen-Kaesbach
Gabriele
G
Hendriks
Yvonne
Y
Kimonis
Virginia
V
Laframboise
Rachel
R
Laissue
Paul
P
Leppig
Kathleen
K
Leroy
Bart P
BP
Miller
David T
DT
Mowat
David
D
Neumann
Luitgard
L
Plomp
Astrid
A
Van Regemorter
Nicole
N
Wieczorek
Dagmar
D
Veitia
Reiner A
RA
De Paepe
Anne
A
De Baere
Elfride
E
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
D018389:Codon, Nonsense; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors