Locus BPES FOXL2
Disease ID
BPES
Gene ID
FOXL2
Updated
Aug 24, 2026
v2.26.0
v2.26.0
Other gene loci
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Clinical Links
Bioinformatical Links
Disease
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Name Blepharophimosis, epicanthus inversus, and ptosis
Inheritance
Description Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) is an ophthalmic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus, that can appear associated with (type I) or without premature ovarian failure (POF) (type II)1 .
Prevalence
0.3 50,000
Age of Onset 0 (birth)
HPO Terms
HP:0000013 Hypoplasia of the uterusHP:0000141 AmenorrheaHP:0000218 High palateHP:0000252 MicrocephalyHP:0000286 EpicanthusHP:0000378 Cupped earHP:0000431 Wide nasal bridgeHP:0000482 MicrocorneaHP:0000486 StrabismusHP:0000506 TelecanthusHP:0000508 PtosisHP:0000537 Epicanthus inversusHP:0000540 HypermetropiaHP:0000545 MyopiaHP:0000568 MicrophthalmiaHP:0000581 BlepharophimosisHP:0000639 NystagmusHP:0000664 SynophrysHP:0000769 Abnormality of the breastHP:0000837 Increased circulating gonadotropin levelHP:0000858 Irregular menstruationHP:0002225 Sparse pubic hairHP:0002553 Highly arched eyebrowHP:0005280 Depressed nasal bridgeHP:0008209 Premature ovarian insufficiencyHP:0008222 Female infertilityHP:0011481 Abnormal lacrimal duct morphologyHP:0045025 Narrow palpebral fissure
Association
Mendelian
Locus
Details 14 repeats appears highly constrained in humans: homozygous expansions from 14 polyalanines to 19 lead to disease, which can be limited to isolated palpebral defects5 . Heterozygous expansions to 24 polyalanines also lead to disease5 . Locus start can differ between catalogs, which can affect genotyping.
Mechanism
GoF/LoF
Detection These expansions are generally within the standard short-read sequencing flanking region and show up with dedicated STR callers, though allelic dropout has been reported6 . PCR based assays with subsequent capillary electrophoresis have accurately detected this expansion when used with a GC-enhancing co solvent7 .
Year Year first published 20034
Location in Gene
Coding Exon 1
Gene Strand
Alleles
Ref. Motif Reference motif, reference orientation
GCN
Ranges
Benign (ref.) Benign motif, reference orientation
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Benign (gene) Benign motif, gene orientation
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Pathogenic (ref.) Pathogenic motif, reference orientation
NGC
Pathogen. (gene) Pathogenic motif, gene orientation
GCN
Unknown (ref.) Unknown motif, reference orientation
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Unknown (gene) Unknown motif, gene orientation
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Interruption (ref.) Interruption motif, reference orientation
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Interrup. (gene) Interruption motif, gene orientation
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gnomAD
Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.
References
Direct supporting references for info on this page.
1
Ontology Lookup Service (OLS)
mondo:00072012
Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome
Charlotte,Matton, Arnaud,Thomaes, Martine,Cools, Hannah,Verdin, Elfride,De Baere
GeneReviews® · 1993-01-01
genereviews:NBK14413
Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions
Stephanie E.,Wallace, Lora JH,Bean
GeneReviews® [Internet] · 2022-10-20
genereviews:NBK5351484
FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation.
Elfride,De Baere, Diane,Beysen, Christine,Oley, Birgit,Lorenz, Julie,Cocquet, Paul,De Sutter, Koen,Devriendt, Michael,Dixon, Marc,Fellous, Jean-Pierre,Fryns, Arturo,Garza, Christoffer,Jonsrud, Pasi A,Koivisto, Amanda,Krause, Bart P,Leroy, Françoise,Meire, Astrid,Plomp, Lionel,Van Maldergem, Anne,De Paepe, Reiner,Veitia, Ludwine,Messiaen
American journal of human genetics · 2003-01-14
pmid:125298555
A recurrent polyalanine expansion in the transcription factor FOXL2 induces extensive nuclear and cytoplasmic protein aggregation.
S,Caburet, A,Demarez, L,Moumné, M,Fellous, E,De Baere, R A,Veitia
Journal of medical genetics · 2004-12-01
pmid:15591279Additional Literature
Additional literature related to this locus.
Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem
repeats, and disease, in medline format)
The combination of polyalanine expansion mutation and a novel missense substitution in transcription factor FOXL2 leads to different ovarian phenotypes in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) patients.
Jiayan,Fan, Yixiong,Zhou, Xiaolin,Huang, Leilei,Zhang, Yuting,Yao, Xin,Song, Junzhao,Chen, Jifan,Hu, Shengfang,Ge, Huaidong,Song, Xianqun,Fan
Human reproduction (Oxford, England) · 2012-08-27
pmid:22926839Differential aggregation and functional impairment induced by polyalanine expansions in FOXL2, a transcription factor involved in cranio-facial and ovarian development.
Lara,Moumné, Aurélie,Dipietromaria, Frank,Batista, Ayhan,Kocer, Marc,Fellous, Eric,Pailhoux, Reiner A,Veitia
Human molecular genetics · 2007-12-24
pmid:18158309A novel polyalanine expansion in FOXL2: the first evidence for a recessive form of the blepharophimosis syndrome (BPES) associated with ovarian dysfunction.
Jeyabalan,Nallathambi, Lara,Moumné, Elfride,De Baere, Diane,Beysen, Kim,Usha, Periasamy,Sundaresan, Reiner A,Veitia
Human genetics · 2006-11-07
pmid:17089161Definition of the blepharophimosis, ptosis, epicanthus inversus syndrome critical region at chromosome 3q23 based on the analysis of chromosomal anomalies.
C T,Lawson, C,Toomes, A,Fryer, M J,Carette, G M,Taylor, Y,Fukushima, M J,Dixon
Human molecular genetics · 1995-05-01
pmid:7633459