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Hereditary Hemorrhagic Telangiectasia Panel

The Hereditary Hemorrhagic Telangiectasia Panel is a comprehensive next-generation (NGS) panel that can be used to confirm a clinical diagnosis of hereditary hemorrhagic telangiectasia or identify at-risk individuals.

Hereditary hemorrhagic telangiectasia is a condition characterized by circulatory system abnormalities called arteriovenous malformations, which occur when arteries flow directly into veins, rather than into capillaries. These malformations result in increased pressure in affected blood vessels, which can result in episodes of severe bleeding. One of the most common symptoms of hereditary hemorrhagic telangiectasia is nosebleeds. Hemorrhages that occur in the brain, liver, lungs, or other organs can be life-threatening.

Included Disorders

This panel includes genes associated with:

  • Hereditary hemorrhagic telangiectasia
  • Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome

Prevalence

The prevalence of hereditary hemorrhagic telangiectasia is between 1 in 5,000 to 1 in 8,000 individuals (Giovani and Shovlin, 2009)

Inheritance and Penetrance

Hereditary hemorrhagic telangiectasia is inherited in an autosomal dominant manner, and exhibits age-related penetrance and variable expressivity (McDonald and Pyeritz, 2000).

Clinical Sensitivity

Pathogenic variants can be identified in more than 80% of hereditary hemorrhagic telangiectasia cases (Prigoda et al, 2006). The Hereditary Hemorrhagic Telangiectasia Panel includes all of the most common genes associated with this condition.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity and specificity of the assay is >99%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Multiple arteriovenous malformations
  • Recurrent unexplained nosebleeds
  • Risk assessment for asymptomatic family members of proband with molecular diagnosis

Included Genes (4)

ACVRL1 ENG RASA1 SMAD4

 

Additions to Comprehensive Panel

Emerging evidence genes can also be added onto the Hereditary Hemorrhagic Telangiectasia Panel. These genes do not have a clear association with hereditary hemorrhagic telangiectasia, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence Gene (1)

GDF2

 

References

  1. Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet. 2009;17(7):860-71.
  2. McDonald J, Pyeritz RE. Hereditary Hemorrhagic Telangiectasia. 2000 Jun 26 [Updated 2017 Feb 2]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  3. Prigoda NL, Savas S, Abdalla SA, et al. Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations. J Med Genet. 2006;43(9):722-8.