The humanFOXL2 mutation database

Abstract

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES; MIM# 110100) is an autosomal dominant genetic condition in which an eyelid malformation is associated (type I) or not associated (type II) with premature ovarian failure (POF). In 2001, mutations in the FOXL2 gene, encoding a forkhead transcription factor, were shown to cause both BPES type I and II. Since then, a number of reports have appeared that describe intragenic FOXL2 mutations in BPES patients. In addition, a few FOXL2 variants have been reported in isolated POF patients and XX males. Previously, our group has described a large number of FOXL2 mutations, thereby demonstrating the existence of two mutational hotspots in FOXL2, intra- and interfamilial phenotypic variability in BPES families, and genotype-phenotype correlations for a number of mutations in BPES patients. Here we describe a locus-specific Human FOXL2 Mutation Database (http://medgen.ugent.be/foxl2/), created using the MuStaR software. Our database contains general information about the FOXL2 gene, as well as details about 135 intragenic mutations and variants of FOXL2, obtained from published papers, abstracts of meetings, and from unpublished data produced by our group. Not included in the current version of the database are variants residing outside the coding region of FOXL2 and molecular cytogenetic rearrangements of the FOXL2 locus. The Human FOXL2 Mutation Database was created to provide a unique publicly available online resource of information about human FOXL2 mutations/variants associated with BPES and POF. It allows remote users to submit new mutations to the database and to query the database using a web form. It will facilitate evaluation of the pathogenicity of a particular mutation, as it contains data about disease-causing mutations and polymorphisms in BPES and isolated POF patients, and a link to the known FOXL2 orthologs. Moreover, it will allow us to establish more accurate genotype-phenotype correlations, since clinical information is contained in the database.

FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases

“…Germline mutations in FOXL2 lead to the development of blepharophimosis, ptosis and epicanthus inversus syndrome, with or without accompanying premature ovarian failure (POF) (22). In addition, FOXL2 has also been implicated in sporadic POF (23,24). Indeed, somatic mutations located in the forkhead domain of FOXL2 have been associated with the development of AGCT.…”

Array Comparative Genomic Hybridization Profiling Analysis Reveals Deoxyribonucleic Acid Copy Number Variations Associated with Premature Ovarian Failure

“…Autosomal genes can also be involved in POF. Indeed, mutations of the FSHR (5, 6), ATM, AIRE, GALT1, GDF9 (4,7), FOXO3a (8), NOBOX (9), INHA, NOG, FOXL2 (10), and NR5A1 (11) have been described. Two studies have suggested that PTH-responsive B1 gene and progesterone receptor membrane component-1 could be associated with POF (12,13).…”

A recurrent polyalanine expansion in the transcription factor FOXL2 induces extensive nuclear and cytoplasmic protein aggregation

“…4 5 Expansions of the polyAla tract from 14 to 24 alanines account for 30% of the reported FOXL2 mutations and lead mainly to BPES type II. 3 To date, four different FOXL2 mutations resulting in polyAla expansions have been reported (details at the human FOXL2 mutation database at http://medgen.ugent.be/foxl2; see also Beysen et al 6 ). The most frequent of these mutations is the recurrent 30 bp duplication g.909_938dup (c.672_701dup; p.A224_A234dup).…”