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  • Test code: 04723
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Axenfeld-Rieger Panel

Test description

The Invitae Axenfeld-Rieger Panel analyzes two genes, FOXC1 and PITX2, that are associated with Axenfeld-Rieger syndrome (ARS). Genetic testing of these genes may help confirm clinical diagnosis and provide information for recurrence-risk estimation and counseling.

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Primary panel (2 genes)

FOXC1 PITX2

Add-on Aniridia Gene (1 gene)

Aniridia may be diagnosed as severe iris hypoplasia associated with ARS. The PAX6 gene can be included for testing at no additional charge.

PAX6

  • Axenfeld-Rieger syndrome
    • Axenfeld anomaly
    • iridogoniodysgenesis
    • Peters anomaly
    • Rieger anomaly
    • Rieger syndrome

Axenfeld-Rieger syndrome (ARS) refers to overlapping heterogeneous disorders that are primarily characterized by an ophthalmological abnormality but can also include comorbidities such as dysmorphic facial features, abnormal dentition, and, less commonly, heart defects, hearing loss, and pituitary function-related delayed growth. Abnormal development of the anterior segment of the eye manifests as iris hypoplasia or corectopia and anteriorly displaced Schwalbe’s line with iridocorneal adhesions. Nearly half of affected individuals develop glaucoma. Affected individuals may exhibit different degrees of abnormality in each eye.

Pathogenic changes in FOXC1 and PITX2 account for 15%–40% of ARS cases.

Axenfeld-Rieger syndrome is inherited in an autosomal dominant pattern.

Axenfeld-Rieger syndrome is a completely penetrant disorder.

The prevalence of Axenfeld-Rieger syndrome is estimated at 1 in 200,000 individuals.

  1. Alward, WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am. J. Ophthalmol. 2000; 130(1):107-15. PMID: 11004268
  2. Cella, W, et al. Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma. Invest. Ophthalmol. Vis. Sci. 2006; 47(5):1803-9. PMID: 16638984
  3. Dressler, S, et al. Dental and Craniofacial Anomalies Associated with Axenfeld-Rieger Syndrome with PITX2 Mutation. Case Rep Med. 2010; 2010:621984. PMID: 20339518
  4. Idrees, F, et al. A review of anterior segment dysgeneses. Surv Ophthalmol. 2006; 51(3):213-31. PMID: 16644364
  5. Orphanet. Axenfeld-Rieger syndrome. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=782 Accessed February 2016.
  6. Reis, LM, et al. PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur. J. Hum. Genet. 2012; 20(12):1224-33. PMID: 22569110
  7. Strungaru, MH, et al. Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest. Ophthalmol. Vis. Sci. 2007; 48(1):228-37. PMID: 17197537
  8. Tümer, Z, Bach-Holm, D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur. J. Hum. Genet. 2009; 17(12):1527-39. PMID: 19513095
  9. Weisschuh, N, et al. Clinical utility gene card for: Axenfeld-Rieger syndrome. Eur. J. Hum. Genet. 2011; 19(3). PMID: 20940740
  10. Weisschuh, N, et al. Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations. Invest. Ophthalmol. Vis. Sci. 2006; 47(9):3846-52. PMID: 16936096

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
FOXC1 NM_001453.2
PAX6 NM_000280.4; NM_001604.5
PITX2 NM_153427.2; NM_000325.5; NM_153426.2