Diagnostic Test Directory

Molecular Genetics Laboratory

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Blepharophimosis-ptosis-epicanthus inversus syndrome, BPES (FOXL2 Sequence and Deletion Analysis)

  • LIS Mnemonic: MBFOXL2SCRN


    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    5 ml whole blood or 2 ug DNA

    Minimum Required

    3 ml


    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.


    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm


4-6 weeks


81479 x 2

Disease Information

Clinical Features:

The primary clinical signs of BPES are blepharophimosis, ptosis and epicanthus inversus, although a variety of ocular and non-ocular features have been described. The association with amenorrhoea, infertility, and elevated gonadotropin levels in females has been noted. Based on the phenotype, two different types of BPES have been described. In BPES type I, eyelid malformations are associated with premature ovarian failure (POF), whereas in BPES type II, only the eyelid defect is observed. Mutations in the FOXL2 gene, a putative forkhead transcription factor gene, have been shown to cause both types of BPES.

Molecular Genetics:

The FOXL2 gene is located on chromosome 3q23. The inheritance pattern is autosomal dominant. Intragenic point mutations have been found in about 70% of BPES patients. They include premature stop codons, missense mutations, expansions of the region encoding the poly alanine domain and frameshift mutations leading to a shorter or longer protein. Thirty three percent of the point mutations detected in the coding region result in an expansion of the poly alanine tract of FOXL1, and are mainly responsible for BPES type II. Genomic rearrangements have been found in 16% of patients, including microdeletions encompassing FOXL2 (10%), translocations and deletions involving long-range non-genic conserved sequences far upstream and downstream of FOXL2 (6%). There is considerable intra- and interfamilial phenotypic variability with these mutations (ie., both BPES types can be caused by the same mutation).

Test Methods:

We offer DNA sequence analysis and deletion/duplication testing of the entire coding region of the FOXL2 gene. These tests can be ordered as a panel or individually. PCR amplification and sequence analysis is performed on the coding exon including splice junctions. The patient’s gene sequence is compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay. Large deletions and duplications will be detected using multiplex ligation-dependent probe amplification assay (MLPA). Translocations and deletions involving long-range non-genic conserved sequences far upstream and downstream of FOXL2 will not be detected by this assay (~6%).

Detection Rate:

Point mutations in the FOXL2 gene are detected in 70% of cases with BPES. Deletions in the FOXL2 gene are detected in 10% of cases with BPES. The analytical sensitivity for MLPA and sequencing is close to 100%.

Related Tests:

Known mutation analysis is available to family members for mutations previously identified by sequence analysis.


Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.


The clinical utility of the assay is in confirming the clinical diagnosis of BPES in these patients, assessing the risk to other first degree relatives and genotyping at risk family members.

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