Brugada Syndrome (BrS) Subpanel (20)

 

Related Genes: ABCC9, CACNA1C, CACNA2D1, CACNB2, GPD1L, HCN4, KCND3, KCNE3, KCNE5, KCNH2, KCNJ8, PKP2, RANGRF, SCN10A, SCN1B, SCN2B, SCN3B, SCN5A, SLMAP, and TRPM4.

Brugada syndrome (BrS) is a channelopathy caused by genetic changes in transmembrane ion channels resulting in cardiac conduction abnormalities in the absence of structural heart abnormalities. Conduction abnormalities include a distinctive electrocardiogram (ECG) pattern (ST-segment elevation) and a high risk for ventricular arrhythmias. These may be transient in nature and can be evoked by pharmacological sodium channel blockade.

Clinical presentations include fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep. Episodes can begin any time in early infancy through late adulthood. Sudden death typically occurs around age 40. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than 1 year. BrS is estimated to affect 1 out of every 2,000 people.

BrS is typically inherited in an autosomal dominant manner (the exception being KCNQ5, which is associated with X-linked inheritance).

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: The Comprehensive Immunodeficiency Panel and subpanels 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: Targeted familial mutation analysis or single gene testing is available for any of the genes on this panel. 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.


Specimen Requirements

 

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.

Newborn/child:
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.

Prenatal:
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

 

Extracted DNA

  • A minimum of 10 μL DNA (50-250 ng/μL) is required for testing. 20 μL DNA (50-350 ng/μL) is recommended

 

Saliva

  • 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

 

Cheek Swab

  • 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.

Ordering Information

 

Shipping:
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:

Sema4
62 Southfield Ave
Stamford, CT 06902

 

Contact:

gc@sema4.com
Tel: 800-298-6470
Fax: 646-859-6870


Turnaround Time:
Results are reported in 3-4 weeks (for postnatal samples) from the receipt of the specimen.

 

Related Tests:

 

Resources: