Brugada Syndrome via the GPD1L Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9955 GPD1L 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9955GPD1L81479 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Brugada syndrome (BrS) is a potentially life-threating arrhythmia disorder without structural abnormalities, characterized by dizziness, syncope, nocturnal agonal respiration and sudden death. The classic electrocardiographic findings associated with Brugada Syndrome include ST segment elevation in leads V1 to V3, right bundle branch block, first degree AV block, and intraventricular conduction delay. Brugada syndrome is much more common in men than in women and many people who have Brugada syndrome don't have any symptoms. Symptoms usually manifest during adulthood, but they may appear any time between two days and 80 years of age (Antzelevitch et al. 2005). Brugada syndrome is treatable with preventive measures such as reducing fever, avoiding certain medications and using an implantable cardiac defibrillator (Francis et al. 2005).

Genetics

Brugada syndrome is an autosomal dominant genetic disorder with variable expression, resulting from mutations within genes that encode cardiac ion channels. BrS is also referred to as a “cardiac channelopathy.” Pathogenic variants in 16 genes (CACNA1C, CACNB2, CACNA2D1, GPD1L, KCND3, KCNE3, KCNE5, KCNJ8, HCN4, RANGRF, SCN5A, SCN1B, SCN2B, SCN3B, SLMAP, and TRPM4) influencing sodium and calcium currents in the heart are associated with BrS and account for at least 26%-41% of cases of Brugada syndrome (Kapplinger et al 2010; Crotti et al. 2012). Most patients with Brugada syndrome have inherited a disease-causing variant from a parent, as de novo mutations in BrS are rare (Hedley et al. 2009). So far, all causative variants reported in GPD1L are missense (Human Gene Mutation Database).

The GPD1L gene is composed of eight exons spanning 62 kb at chromosome 3p24–p22 and associated with Brugada Syndrome 2 (Nagase et al. 1995; London et al. 2007). GPD1L encodes glycerol-3-phosphate dehydrogenase 1-like protein and plays a role in regulating cardiac sodium current through modifying SCN5A function (London et al. 2007). Mutants of GPD1L increased glycerol-3-phosphate PKC-mediated  phosphorylation of SCN5A which in turn causes a dysfunction in sodium current  (Valdivia et al. 2009). This GPD1L pathway is demonstrated to be affected by the balance between oxidized and reduced nicotinamide adenine dinucleotide hydrogenase (NADH) (Liu et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the GPD1L gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in SCN5A gene cause 15%-30% of Brugada syndrome based on clinical diagnosis. Pathogenic variants within other genes associated with Brugada syndrome (GPD1L, CACNA1C, CACNB2B, SCN1B, SCN3B, KCNE3,KCNJ8, KCND3,CACNA2D1, MOG1, and HCN4) have been identified in a total of approximately 5% of patients with Brugada syndrome (Kapplinger et al 2010; Crotti et al. 2012). KCNE5, SCN2B, SLMAP and TRPM4 are newly identified genes associated with Brugada syndrome. There is insufficient data to calculate their clinical sensitivities.

Indications for Test

All patients with symptoms suggestive of Brugada syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
GPD1L 611778
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Brugada Syndrome 2 611777

Related Tests

Name
Brugada Syndrome 1 via the SCN5A Gene
Brugada Syndrome via the KCNE3 Gene
Brugada Syndrome via the SCN3B Gene

Citations

  • Antzelevitch C. et al. 2005. Circulation. 111: 659-70. PubMed ID: 15655131
  • Crotti L. et al. 2012. Journal of the American College of Cardiology. 60: 1410-8. PubMed ID: 22840528
  • Crotti L. et al. 2012. Journal of the American College of Cardiology. 60: 1410-8. PubMed ID: 22840528
  • Francis J., Antzelevitch C. 2005. International journal of cardiology. 101: 173-8. PubMed ID: 15882659
  • Hedley PL. et al. 2009. Human mutation. 30: 1256-66. PubMed ID: 19606473
  • Human Gene Mutation Database (Bio-base).
  • Human Gene Mutation Database (Bio-base).
  • Kapplinger JD. et al. 2010. Heart rhythm : the official journal of the Heart Rhythm Society. 7: 33-46. PubMed ID: 20129283
  • Kapplinger JD. et al. 2010. Heart rhythm : the official journal of the Heart Rhythm Society. 7: 33-46. PubMed ID: 20129283
  • Liu M, Sanyal S, Gao G, Gurung IS, Zhu X, Gaconnet G, Kerchner LJ, Shang LL, Huang CL-H, Grace A, London B, Dudley SC. 2009. Cardiac Na+ current regulation by pyridine nucleotides. Circ. Res. 105: 737–745. PubMed ID: 19745168
  • London B, Michalec M, Mehdi H, Zhu X, Kerchner L, Sanyal S, Viswanathan PC, Pfahnl AE, Shang LL, Madhusudanan M, Baty CJ, Lagana S, Aleong R, Gutmann R, Ackerman MJ, McNamara DM, Weiss R, Dudley SC Jr. 2007. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 116: 2260–2268. PubMed ID: 17967977
  • Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H. 1995. Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 37–43. PubMed ID: 7788527
  • Valdivia CR, Ueda K, Ackerman MJ, Makielski JC. 2009. GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A. Am. J. Physiol. Heart Circ. Physiol. 297: H1446–1452. PubMed ID: 19666841

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×