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Long QT Syndrome and Jervell and Lange-Nielsen Syndrome via the KCNE1 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
9193 KCNE1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9193KCNE181479 81479(x2) $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.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Chun-An Chen, PhD

Clinical Features and Genetics

Clinical Features

Long QT syndrome (LQTS) is a heritable channelopathy characterized by an exceedingly prolonged cardiac repolarization that may trigger ventricular arrhythmias (torsade de pointes), recurrent syncopes, seizure, or sudden cardiac death (SCD) (Cerrone et al. 2012). The incidence of LQTS has been estimated between 1 in 2500 and 1 in 7000 in the general population.  LQTS can manifest with syncope and cardiac arrest that is commonly triggered by adrenergic stress, often precipitated by emotion or exercise. Roughly 10% to 15% of patients experience symptoms at rest or during the night (Schwartz et al. 2001). The mean age of onset of symptoms is 12 years, and earlier onset usually is associated with a more severe form of the disease (Priori et al 2004). Inherited LQTS occurs due to mutations in multiple genes such as KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), ANK2(LQT4), KCNE1 (LQT5), KCNE2 (LQT6), KCNJ2(LQT7), CACNA1C(LQT8), CAV3(LQT9), SCN4B(LQT10), AKAP9(LQT11), SNTA1(LQT12) and KCNJ5 (LQT13), but it can also be acquired (acquired LQTS), usually as a result of pharmacological therapy. A small percentage of cases of LQTS occur in people who have an underlying variation in the KCNE1 gene.Jervell and Lange-Nielsen Syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually greater than 500 msec. If untreated, the irregular heartbeats can lead to life-threatening ventricular arrhythmias, and a high risk of sudden cardiac death (Schwartz et al. 2006). Jervell and Lange-Nielsen syndrome prevalence remains largely unknown due to the high mortality in infancy and lack of comprehensive neonatal screening methods. KCNQ1 or KCNE1 are the only two genes in which pathogenic variants are known to cause JLNS. JLNS is usually detected during early childhood and is inherited as an autosomal recessive genetic disorder. More than half of the untreated cases of JLNS result in death before the age of 15.

Genetics

Jervell and Lange-Nielsen Syndrome is inherited in an autosomal recessive pattern. About 90 percent of Jervell and Lange-Nielsen syndrome cases are caused by mutations in the KCNQ1 gene. KCNE1 mutations are responsible for the remaining 10 percent of cases (Schwartz et al. 2006; Tyson et al. 2000). The subtype of Jervell and Lange-Nielsen syndrome caused by mutations in the KCNQ1 gene is called JLNS1. Another  subtype,  JLNS2, is  caused by mutations in the KCNE1 gene, also known as Ward-Romano syndrome, and Long QT syndrome 5. So far, KCNE1 mutations found in JLNS are missense/nonsense (87%) and small deletion/insertion/indels (11%) (Human Gene Mutation Database).KCNE1 (potassium voltage-gated channel, Isk-related family, member 1) belongs to the potassium channel KCNE gene family.  The KCNE1 gene regulates a potassium channel made up of proteins produced by the KCNQ1 gene. KCNE1 and KCNQ1 work together to form a potassium channel that transports positively charged potassium ions out of cells, which is critical for maintaining the normal functions of the inner ear and cardiac muscle (Crump et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants have been found in either KCNQ1 or KCNE1 in 94% of individuals with clinical JLNS undergoing molecular testing. The pathogenic variants may be located in all coding exons. Current experience indicates that 33% are compound heterozygotes (Schwartz et al 2006). About 90 percent of Jervell and Lange-Nielsen syndrome cases are caused by mutations in the KCNQ1 gene. KCNE1 mutations are responsible for the remaining 10 percent of cases (Schwartz et al. 2006; Tyson et al. 2000). Splawski et al (2000) screened 262 unrelated LQTS patients for causative variants in 5 genes: KVLQT1, HERG, SCN5A, KCNE1 and KCNE2. They reported causative variants in 68% of their subjects. Of these, 45% were in HERG, 42% in KVLQT1, 8% in SCN5A, 3% in KCNE1 and 2% in KCNE2.

Gross deletions and duplications in the KCNE1 gene have not been reported in patients with Long QT syndrome and Jervell and Lange-Nielsen syndrome (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the KCNE1 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

All patients with symptoms suggestive of Long QT syndrome/ Jervell and Lange-Nielsen syndrome are candidates for this test.

Gene

Official Gene Symbol OMIM ID
KCNE1 176261
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Long QT Syndrome via the SCN4B Gene

Citations

  • Cerrone M. et al. 2012. Circulation. Cardiovascular genetics. 5: 581-90. PubMed ID: 23074337
  • Crump SM, Abbott GW. 2014. Arrhythmogenic KCNE gene variants: current knowledge and future challenges. Front Genet 5: 3. PubMed ID: 24478792
  • Human Gene Mutation Database (Bio-base).
  • Human Gene Mutation Database (Bio-base).
  • Priori et al. 2004. PubMed ID: 15367556
  • Schwartz et al. 2001. PubMed ID: 11136691
  • Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I. 2006. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 113: 783–790. PubMed ID: 16461811
  • Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I. 2006. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 113: 783–790. PubMed ID: 16461811
  • Schwartz PJ, Spazzolini C, Crotti L, Bathen J, Amlie JP, Timothy K, Shkolnikova M, Berul CI, Bitner-Glindzicz M, Toivonen L, Horie M, Schulze-Bahr E, Denjoy I. 2006. The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome. Circulation 113: 783–790. PubMed ID: 16461811
  • Splawski I. et al. 2000. Circulation. 102: 1178-85. PubMed ID: 10973849
  • Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Christiansen M, Whiteford ML, Bathen J, Aslaksen B, Sørland SJ, Lund O, Pembrey ME, Malcolm S, Bitner-Glindzicz M. 2000. Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen. Hum. Genet. 107: 499–503. PubMed ID: 11140949
  • Tyson J, Tranebjaerg L, McEntagart M, Larsen LA, Christiansen M, Whiteford ML, Bathen J, Aslaksen B, Sørland SJ, Lund O, Pembrey ME, Malcolm S, Bitner-Glindzicz M. 2000. Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen. Hum. Genet. 107: 499–503. PubMed ID: 11140949

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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