Asper Immunogenetics

Hyperinsulinism NGS panel

List of diseases covered by
Renal Cancer NGS panel

Renal Cancer NGS panel

Severe Combined Immunodeficiency NGS panel

List of diseases covered by
Severe Combined Immunodeficiency NGS panel

Neutropenia NGS panel

Malignant Hyperthermia NGS panel

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

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).

Statin-Induced Myopathy targeted mutation analysis 

Indications for genetic testing:

1. Risk assessment for developing statin-induced myopathy
2. Optimizing the statin dose

Statins inhibit the synthesis of cholesterol and promote the production of low density lipoprotein (LDL)-binding receptors in the liver resulting in an unusually marked decrease in the level of LDL, and a modest increase in the level of high density lipoprotein (HDL) circulating in blood plasma. Therefore, statin drugs are the primary pharmacologic treatment for hypercholesterolemia and coronary artery disease worldwide.

Despite their demonstrated safety and efficacy, 25% to 50% of individuals with cardiovascular disease are nonadherent with statin medications after one year. Although there may be multiple contributing factors, many experts report that a contributor to statin nonadherence is associated with side effects, including skeletal muscle toxicity due to poor or compromised metabolism of statin drugs.

Statin-induced myopathy has been associated with SLCO1B1 gene variant NM_006446.4:c.521T>C (rs4149056). The risk of myopathy may be substantially increased in patients who take 80 mg of simvastatin daily, as well as in those who are also receiving certain other drugs.

References:

Ramsey LB et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct;96(4):423-8.
EARCH Collaborative Group et al. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99
Tomaszewski M et al. Statin-induced myopathies. Pharmacol Rep. 2011;63(4):859-66.

Asper Pharmacogenetics

Asper Pharmacogenetics is a collection of genetic tests targeting drug-gene interactions including metabolic response to medications and predisposition to adverse drug reactions.

Extensive research has been carried out in the past years to determine the relationship between therapeutic drugs and genes. The studies demonstrate the growing importance of genetically guided treatment, especially in the concept of personalized medicine.

Knowledge on genetic aspects determining drug metabolism allows the implementation of genotype-guided prescription and dosing. It can not only improve drug efficacy but also help prevent adverse drug reactions.

Aminoglycoside-Induced Deafness
targeted mutation analysis

Indications for genetic testing:

1. Determination of molecular genetic basis of nonsyndromic sensorineural hearing loss
2. Define etiology of hearing loss after aminoglycoside therapy
3. Detection the carrier status of individuals with family history of maternally-inherited hearing loss with or without aminoglycoside therapy
4. Detection the carrier status of relatives with a known mutation
5. Genetic counseling

Aminoglycosides are a group of pharmacologic agents that have been shown to have toxic effects to the cochleovestibular system.

Cochlear toxicity can result in sensorineural hearing loss and dysequilibrium. Hearing loss is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin.

Predisposition to aminoglycoside, caused by aminoglycoside exposure is known to be associated with pathogenic variants in the MT-RNR1 gene. Nonsyndromic mitochondrial hearing loss and deafness is transmitted by maternal inheritance.

References:

Bates DE. Aminoglycoside ototoxicity. Drugs Today (Barc) 2003;39:277–85.
Hirvonen TP, Minor LB, Hullar TE, Carey JP. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla. J Neurophysiol. 2005 Feb. 93(2):643-55.
Pandya A. Nonsyndromic Hearing Loss and Deafness, Mitochondrial. GeneReviews® 2004 Oct 22 (Updated 2014 July 3)

List of non-coding variants covered by
Microcephaly NGS panel

List of non-coding variants covered by
Hereditary Spastic Paraplegia NGS panel

List of non-coding variants covered by
Frontotemporal Dementia NGS panel

List of non-coding variants covered by
Microcephaly NGS panel

List of non-coding variants covered by
Tuberous Sclerosis NGS panel

List of non-coding variants covered by
Tuberous Sclerosis NGS panel

List of diseases covered by
Neurofibromatosis NGS panel

List of diseases covered by Melanoma NGS panel

List of diseases covered by
Frazer Syndrome NGS panel

List of diseases covered by Melanoma NGS panel

List of non-coding variants covered by
Congenital Muscular Dystrophy NGS panel

List of diseases covered by
Congenital Muscular Dystrophy NGS panel

Congenital Muscular Dystrophy
NGS panel

List of non-coding variants covered by
Cornelia de Lange Syndrome NGS panel

List of diseases covered by
Cornelia de Lange Syndrome NGS panel

List of non-coding variants covered by
Cornelia de Lange Syndrome NGS panel

List of diseases covered by
Left Ventricular Noncompaction Cardiomyopathy
NGS panel

Left Ventricular Noncompaction Cardiomyopathy
NGS panel

List of non-coding variants covered by
Charcot-Marie-Tooth NGS panel

List of non-coding variants covered by
Dystonia NGS panel

List of non-coding variants covered by
Hereditary Ataxia NGS panel

Congenital Fibrosis of Extraocular Muscles NGS panel

List of diseases covered by
Hypomagnesemia NGS panel

Hypomagnesemia NGS panel