Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication
Use for individuals with clinical features of HHT, if sequential testing is desired. Follow with SMAD4 testing if no causative variant is identified in ACVRL1 or ENG.
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Background Information for Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication
Characteristics: Recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), and arteriovenous malformations (lung, brain, liver, spine).
Inheritance: Autosomal dominant.
Penetrance: Approaches 100 percent by age 40.
Cause: Pathogenic variants in ENG, ACVRL1/ALK1, SMAD4, BMP9/GDF2 or other unidentified gene(s).
Genes Tested: ENG and ACVRL1
Clinical Sensitivity: Approximately 85 percent
Methodology: Bidirectional sequencing of the coding regions and intron-exon boundaries of ENG and ACVRL1, the 5' untranslated region of ENG, and a region of ACVRL1 intron 9 encompassing the CT-rich variant hotspot region. Multiplex ligation-dependent probe amplification (MLPA) of the coding regions of ACVRL1 and ENG.
Analytic Sensitivity: 99 percent for sequencing and 90 percent for MLPA.
Analytic Specificity: 99 percent for sequencing and 98 percent for MLPA.
Limitations: Diagnostic errors can occur due to rare sequence variations. The breakpoints of large deletions/duplication cannot be determined. Regulatory region, intronic mutations, and mutations in genes other than ENG and ACVRL1 will not be detected.
Laboratory Developed Test (LDT)
81406; 81405; 81479
|Component Test Code*||Component Chart Name||LOINC|
|0051350||HHT, Sequencing and Deletion/Duplication|
|2001355||HHT, Seq-Del/Dup - Specimen||31208-2|
- Activin A Receptor, Type II-Like I
- ACVRL1 Gene; ALK1 Gene
- Arteriovenous Malformations
- AVM genetic testing
- HHT molecular testing