Malignant Hyperthermia NGS panel

Malignant Hyperthermia NGS panel

Genes
(full coding
region):
CACNA1S, RYR1, STAC3

Lab method: NGS panel with CNV analysis

TAT: 6-9 weeks

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

  1. Clinical episode of malignant hyperthermia (MH)
  2. Positive caffeine/halothane contracture test
  3. Relative with a positive contracture test or a known MH-causing variant
  4. Unexplained death with signs of MH during or immediately after anesthesia
  5. Exercise-related rhabdomyolysis and/or heat stroke

Malignant hyperthermia is an inherited pharmacogenetic disorder of calcium regulation resulting in uncontrolled skeletal muscle hypermetabolism.

Manifestations of MH are triggered by certain volatile anesthetics (i.e. halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with succinylcholine, a depolarizing muscle relaxant. The triggering substances initiate uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate.

MH clinical manifestations are hyperthermia, hypercapnia, tachycardia, acidosis, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure.

In nearly all cases, the first manifestations of MH occur in the operating room, MH may also occur in the early postoperative period. Recent studies show that some individuals with MH will also develop the disorder with exercise and/or on exposure to hot environments. Without prompt treatment with dantrolene sodium, mortality is extremely high.

MH is an autosomal dominant disorder.

References:

Riazi S, Kraeva N, Hopkins PM. Updated guide for the management of malignant hyperthermia. Can J Anaesth. 2018;65:709–21.
Rosenberg H et al. Malignant Hyperthermia Susceptibility. GeneReviews® Initial Posting: December 19, 2003; Last Update: January 16, 2020.
Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: A review. Orphanet J Rare Dis. 2015;10:93.

Antidepressants PGx test

We are pleased to announce that Asper Biogene has launched a new pharmacogenetic test – Antidepressants PGx – for assessing metabolic response to antidepressant medications.

Antidepressants PGx test includes carefully selected and strictly evidence-based genetic markers. The test provides dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) based on guidelines published by Clinical Pharmacogenetics Implementation Consortium (CPIC). Read more at www.asperbio.com/asper-pharmacogenetics/antidepressants-pgx/

Antidepressants PGx

Antidepressants PGx

Genes: CYP2C19, CYP2D6

Lab method: NGS, Long PCR

TAT: 10-15 working days

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

  1. Optimization of drug therapy to ensure maximum efficacy with minimal adverse effects
  2. Dose adjustments or an alternative agent selection

The test provides an interpretation of CYP2D6 and CYP2C19 genotyping results and drug metabolism phenotypes. Dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) based on Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines are included in the test report.

SSRIs are primary treatment options for major depressive and anxiety disorders. The SSRIs selectively increase serotonergic activity by decreasing presynaptic serotonin reuptake. Therapeutic outcome is dependent on the polymorphisms in CYP2D6 and CYP2C19 genes influencing the metabolism of SSRIs, thereby affecting drug efficacy and safety. Approximately 50% of patients diagnosed with major depressive disorder will fail initial SSRI therapy.

Common adverse effects induced by this drug class include central nervous system effects (e.g., insomnia, headache), gastrointestinal dysfunction, and sexual dysfunction. Serious adverse events such as arrhythmias caused by QT prolongation have been described in individuals who are CYP2C19 poor metabolizers and are prescribed citalopram.

Tricyclic antidepressants (TCAs) are mixed serotonin and norepinephrine reuptake inhibitors used to treat several diseases including depression, obsessive-compulsive disorder, and neuropathic pain in addition to migraine prophylaxis. CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of TCAs. Patients may be predisposed to treatment failure or adverse effects due to genetic variation in CYP2D6 gene altering drug clearance or in CYP2C19 gene altering the ratio of parent drug to metabolites. Common adverse effects include anticholinergic, central nervous system and cardiac effects.

Utilizing pharmacogenetic results to guide depression therapy could improve treatment response and decrease the occurrence of adverse events.

References:

Hicks, J. K., K. Sangkuhl, J. J. Swen, V. L. Ellingrod, D. J. Müller, K. Shimoda, J. R. Bishop, et al. 2017. “Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.”
Hicks, J. K., J. R. Bishop, K. Sangkuhl, D. J. Muller, Y. Ji, S. G. Leckband, J. S. Leeder, et al. 2015. “Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors.”
Funk, K.A. & Bostwick, J.R. A comparison of the risk of QT prolongation among SSRIs. Ann. Pharmacother. 47, 1330–1341 (2013).