Hereditary Hemorrhagic Telangiectasia (ACVRL1 and ENG) Sequencing and Deletion/Duplication with Reflex to Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication
2009008
Ordering Recommendation
Appropriate test when clinical/family history is classic for HHT.
Mnemonic
HHT REFLEX
Methodology
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
Within 35 days  
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
Submit With Order
Specimen Required
Patient Preparation
  
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 2 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
  
Remarks
  
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report  
Interpretive Data
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).
Incidence:
1:5,000-10,000
Inheritance:
Autosomal dominant.
Penetrance:
Approaches 100 percent by age 40.
Cause:
Mutations in endoglin (ENG), activin A receptor type II-like 1 (ACVRL1 or ALK1), SMAD4 or other unidentified gene(s).
Clinical Sensitivity:
Approximately 85 percent
Methodology:
Bidirectional sequencing of ENG and ACVRL1 -all exons and exon/intron boundaries, including the 5' untranslated region of ENG; Multiplex Ligation-dependent Probe Analysis (MLPA) to detect large ENG and ACVRL1 gene deletion/duplication; oligonucleotide probes cover all ENG and ACVRL1 coding exons.
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.




Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS  
Note
If the results of this test do not explain the clinical scenario, then Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication testing will be added. Additional charges apply.
CPT Code(s)
81405 (ENG); 81406 (ENG); 81479 x2; if reflexed add 81405 (SMAD4); 81406 (SMAD4)
Components
Component Test Code*Component Chart Name
2009010HHT Seq/DelDup Interpretation
2009011HHT Seq/DelDup Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases