Progressive Myoclonic Epilepsy via the GOSR2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes
4161 GOSR2$640 8147981479,81479 Add to Order

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Progressive myoclonic epilepsy 6 (EPM6) is a neurological disorder characterized by early onset ataxia and myoclonic seizures. The first symptom of EPM6 is ataxia with onset around 2 years of age. Myoclonic seizures begin in early childhood, and patients exhibit multiple seizure types including: generalized tonic clonic seizures, absence seizures, and drop attacks. Seizures are photosensitive and are worsened by psychological stress and physical movement. EEG reveals generalized spike and wave discharges. Ataxia and myoclonus are progressive with patients becoming wheelchair bound in their early teens. Many EPM6 patients have scoliosis or other skeletal abnormalities. In some patients serum levels of creatine kinase are elevated (median 734 IU), but patients have a normal muscle biopsy (Boisse Lomax et al. 2013; van Egmond et al. 2014). Cognition is preserved, and MRI is largely normal; in one case autopsy revealed slight cerebral atrophy (Corbett et al. 2011). Death typically occurs in the 3rd or 4th decade.

Genetics

EPM6 is inherited in an autosomal recessive manner and is caused by mutations in the GOSR2 gene. A founder mutation, c.430G>T (p.Gly144Trp), exists in the Dutch population (Corbett et al. 2011; Boisse Lomax et al. 2013; van Egmond et al. 2014).

The GOSR2 protein is a member of the Qb-SNARE family of vesicle docking proteins. SNARE complexes form on opposing membranes and aid in membrane fusion in the secretory and endosomal pathways (Xu et al. 2000). The p.Gly144Trp variant alters a conserved residue in the Q-SNARE domain of GOSR2. In vitro studies demonstrate that the p.Gly144Trp mutation disrupts localization of GOSR2 to the Golgi (Corbett et al. 2011). Defects in vesicle trafficking and possibly neurotransmitter release may underlie the epilepsy phenotype of the GOSR2 variant.

Testing Strategy

This test provides full coverage of all coding exons of the GOSR2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing and CNV

The pathogenic c.430G>T GOSR2 variant was identified in ~7% (12 of 159) and ~11% (5 of 46) of patients with genetically unresolved diagnoses of PME or PMA; many patients homozygous for the c.430G>T variant were of Dutch or German ancestry (Boisse Lomax et al. 2013; van Egmond et al. 2014).

Indications for Test

GOSR2 sequencing should be considered for patients with a diagnosis of progressive myoclonic epilepsy (PME), progressive myoclonic ataxia (PMA), or Ramsay Hunt syndrome, especially if they are of Dutch ancestry (van Egmond et al. 2014). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GOSR2.

Gene

Official Gene Symbol OMIM ID
GOSR2 604027
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epilepsy, Progressive Myoclonic 6 AR 614018

Related Tests

Name
Early Infantile Epileptic Encephalopathy Panel
Epilepsy and Seizure Plus Panel

Citations

  • Boisse Lomax L, Bayly MA, Hjalgrim H, Moller RS, Vlaar AM, Aaberg KM, Marquardt I, Gandolfo LC, Willemsen M, Kamsteeg E-J, O’Sullivan JD, Korenke GC, et al. 2013. “North Sea” progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation. Brain 136: 1146–1154. PubMed ID: 23449775
  • Corbett MA, Schwake M, Bahlo M, Dibbens LM, Lin M, Gandolfo LC, Vears DF, O’Sullivan JD, Robertson T, Bayly MA, Gardner AE, Vlaar AM, et al. 2011. A Mutation in the Golgi Qb-SNARE Gene GOSR2 Causes Progressive Myoclonus Epilepsy with Early Ataxia. The American Journal of Human Genetics 88: 657–663. PubMed ID: 21549339
  • van Egmond ME, Verschuuren-Bemelmans CC, Nibbeling EA, Elting JWJ, Sival DA, Brouwer OF, Vries JJ de, Kremer HP, Sinke RJ, Tijssen MA, Koning TJ de. 2014. Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation. Mov. Disord. 29: 139–143. PubMed ID: 24458321
  • Xu D, Joglekar AP, Williams AL, Hay JC. 2000. Subunit Structure of a Mammalian ER/Golgi SNARE Complex. Journal of Biological Chemistry 275: 39631–39639. PubMed ID: 11035026

Ordering/Specimens

Ordering Options

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.

Specimen Types

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