Hereditary Hemorrhagic Telangiectasia (HHT) Subpanel (5)
Related Genes: ACVRL1, ENG, GDF2, RASA1, and SMAD4
Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by blood vessel malformations that may result in abnormalities that affect the liver, lungs, brain, and spinal cord. Individuals with HHT may experience recurrent nosebleeds, gastrointestinal bleeding, anemia, difficulty breathing, episodes of coughing up blood, headaches, and seizures.
HHT is inherited in an autosomal dominant manner and has an estimated prevalence of 1-5/10,000.
Clinical Utility: Genetic testing of an individual may be indicated to distinguish hereditary disorder from acquired (non-genetic) causes, provide information on the likelihood of related health issues, guide clinical management, and establish disease risk to other family members and future generations.
Methods: Hereditary hemorrhagic telangiectasia (HHT) panel offered by Sema4 primarily utilizes next-generation sequencing (NGS) to identify variants within the genes analyzed. Copy number variant (CNV) detection by NGS is also utilized to increase diagnostic yield. Supplemental and confirmatory technology used in this panel may include targeted genotyping, multiplex ligation-dependent probe amplification (MLPA), exon array, quantitative PCR, and Sanger sequencing. Ultra high-resolution medical exon array (UHRMEA) is available for deletion/duplication studies of gene(s) within this panel as either reflex (add-on), concurrent, or standalone test. UHRMEA provides single exon level coverage for the majority of the exons within this panel. Variant classification and interpretation are performed based on the American College of Medical Genetics Standards and guidelines for the interpretation of sequence variants.
Targeted Testing: Prenatal diagnosis is also available for known familial variants; please contact our laboratory at 800-298-6470 to discuss prior to sending any prenatal samples.
Postnatal blood samples:
2 yellow-top (ACD-A or ACD-B) or 2 lavender-top (EDTA) tubes, 5-10 mL of blood from the patient are required. One blood tube from both parents is requested.
1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) tube, 2 mL of blood from the patient are required. Additionally, 1 yellow-top (ACD-A or ACD-B) or 1 lavender-top (EDTA) 5-10 mL tube of blood from both parents is requested.
Please inquire with lab (800-298-6470 option 2)
Prenatal testing for a known familial variant:
- Two confluent T-25 flasks of cultured cells from amniotic fluid or chorionic villi
- >4 mg of direct chorionic villi tissue
- 15 mL of direct amniotic fluid
- 5-10 mL of blood in an EDTA tube (lavender top) is required from each biological parent. Parental blood samples may be used for maternal cell contamination studies or confirmation studies.
- Send in previous report of known familial variant with specimen
- A minimum of 10 μL DNA (50-250 ng/μL) is required for testing. 20 μL DNA (50-350 ng/μL) is recommended
- Saliva specimens are accepted upon request. Please contact our laboratory to obtain saliva kits
- Saliva samples should be collected in Oragene DNA (OG-500) kits by DNA Genotek
- 1 cheek swab specimen collected from ORAGENE kit from the patient is required. 1 cheek swab specimen collected from ORAGENE kit from both parents is requested.
Samples should be kept and shipped refrigerated or at room temperature. Do not freeze specimens.
Include the following with each sample:
- Completed and signed test requisition form and informed consent
- Billing information or payment (include copy of insurance card)
- Contact information for referring physician
- Testing to be performed
- Indication for testing, patient’s family history, ethnic background and prior relevant test results
Send same day or overnight (check for morning delivery) to:
62 Southfield Ave
Stamford, CT 06902
Results are reported in 3-4 weeks (for postnatal samples) from the receipt of the specimen.