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Anterior Segment Dysgenesis via the FOXE3 Gene

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
1821 FOXE3 81479 81479 $580 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
1821FOXE381479 81479 $580 Order Options and Pricing

Pricing Comments

CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

12 days on average for standard orders or 8 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Anterior segment dysgenesis (ASD) is referred to as a developmental disorder in which the anterior segment of the eye including the iris, cornea and trabecular meshwork are affected and result in a spectrum of anomalies such as aniridia, cataracts and glaucoma that lead to visual disability in childhood (Ito and Walter 2014; Brémond-Gignac et al. 2010; Semina et al. 2001).

Genetics

Genes encoding transcription factors such as PAX6, PITX2, FOXC1, FOXE3 and PITX3 have shown to be involved in the control of eye morphogenesis and therefore associated with ASD (Doucette et al. 2011). Homozygous mutations in FOXE3 (forkhead box E3) have been shown to cause non-syndromic, bilateral, total sclerocornea, aphakia, microphthalmia and optic disc coloboma (Ali et al. 2010). Also, dominant FOXE3 mutations have been reported in patients with congenital cataract and aniridia (Semina et al. 2001; Iseri et al. 2009). Dominant variants are those (e.g., c.958T>C (p.*320Argext*72) and c.942dupG (p.Leu315Alafs*117)), which result in extension of the open reading frame beyond the normal stop codon and are reported to have dominant negative effect (Semina et al. 2001; Iseri et al. 2009). Recessive variants (e.g., missense variants) result in altered protein interactions (Iseri et al. 2009). However, a recent functional analysis of six FOXE3 causative variants indicated that three recessive mutants showed loss-of-function, one retained DNA binding activity, whereas two dominant mutants showed altered activity as compared to the wild-type. However, no evidence of dominant negative action was seen in the enlarged proteins due to the c.958T>C and c.942dupG variants (Islam et al. 2015). FOXE3 encodes a forkhead transcription factor and is specifically expressed in the anterior lens epithelium (Semina et al. 2001). So far, about 10 causative variants (missense/nonsense, small deletions and insertions) have been reported in FOXE3 (Human Gene Mutation Database).

Clinical Sensitivity - Sanger Sequencing

Predicting clinical sensitivity for the FOXE3 gene is challenging due to genetic heterogeneity of ASD. However FOXE3 pathogenic variants have been shown to account for 15% (4/26) of bilateral microphthalmia cases [100% of consanguineous families (3/3)], which were negative for SOX2 mutations (Reis et al. 2010).

Testing Strategy

This test involves bidirectional Sanger sequencing of all coding exons and splice sites of the FOXE3 gene. The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results.

Indications for Test

All patients with symptoms suggestive of Anterior segment dysgenesis are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in FOXE3.

Gene

Official Gene Symbol OMIM ID
FOXE3 601094
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Axenfeld-Rieger Syndrome Panel
Cataract Type 11 via the PITX3 Gene
Congenital Cataracts Panel
Familial Thoracic Aortic Aneurysm and Dissection (TAAD) Panel

Citations

  • Ali M, Buentello-Volante B, McKibbin M, Rocha-Medina JA, Fernandez-Fuentes N, Koga-Nakamura W, Ashiq A, Khan K, Booth AP, Williams G, Raashid Y, Jafri H, Rice A, Inglehearn CF, Zenteno JC. 2010. Homozygous FOXE3 mutations cause non-syndromic, bilateral, total sclerocornea, aphakia, microphthalmia and optic disc coloboma. Molecular vision 16: 1162-1668. PubMed ID: 20664696
  • Brémond-Gignac D, Bitoun P, Reis LM, Copin H, Murray JC, Semina EV. 2010. Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia. Molecular vision 16: 1705. PubMed ID: 20806047
  • Doucette L, Green J, Fernandez B, Johnson GJ, Parfrey P, Young T-L. 2011. A novel, non-stop mutation in FOXE3 causes an autosomal dominant form of variable anterior segment dysgenesis including Peters anomaly. Eur J Hum Genet 19: 293–299. PubMed ID: 21150893
  • Human Gene Mutation Database (Bio-base).
  • Iseri S.U. et al. 2009. Human Mutation 30: 1378-86. PubMed ID: 19708017
  • Islam L, Kelberman D, Williamson L, Lewis N, Glindzicz MB, Nischal KK, Sowden JC. 2015. Functional Analysis of FOXE3 Mutations Causing Dominant and Recessive Ocular Anterior Segment Disease. Human Mutation 36: 296–300. PubMed ID: 25504734
  • Ito YA, Walter MA. 2014. Genomics and anterior segment dysgenesis: a review. Clin. Experiment. Ophthalmol. 42: 13–24. PubMed ID: 24433355
  • Reis L.M. et al. 2010. Molecular Vision 16: 768-73. PubMed ID: 20454695
  • Semina E.V. et al. 2001. Human Molecular Genetics. 10: 231-6. PubMed ID: 11159941

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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