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Pontocerebellar Hypoplasia via the VRK1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7379 VRK1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7379VRK181479 81479,81479 $640 Order Options and Pricing

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.

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

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

Pontocerebellar hypoplasias (PCH) are a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by abnormal development of the pons, cerebellum and cerebral cortex; progressive microcephaly; psychomotor developmental delay; and swallowing difficulties (Barth. 1993. PubMed ID: 8147499; Namavar et al. 2011. PubMed ID: 21368912). Several subtypes have been described based on the clinical presentation, progression, and pathological and molecular defects. However, clinical overlapping features among various subtypes have been reported, and some genes have been implicated in more than one subtype, suggesting that PCH constitute a spectrum (Burglen et al. 2012. PubMed ID: 22452838; Samanta and Willis. 2016. PubMed ID: 27570394).

PCH1, previously known as Norman’s disease, is distinguished by a loss of motor neurons in the anterior horn of the spinal cord similar to that observed in spinal muscular atrophy (SMA), resulting in sensory and motor neuropathy. Additional features include severe hypotonia, fasciculation, ataxia, dysplasia, joint contractures, visual abnormalities and hyperventilation. Symptoms are usually apparent at birth, and death usually occurs within the first year of life. However, survival into childhood has been described. Based on the clinical features and electrophysiological and muscle biopsy findings, a number of patients with PCH1 were originally diagnosed with infantile SMA-PCH (Norman. 1961. PubMed ID: 13729575; Rudnik-Schöneborn et al. 2003. PubMed ID: 12548734; Renbaum et al. 2009. PubMed ID: 19646678). PCH1 appears to be rare.

Genetics

All pontocerebellar hypoplasias are transmitted with an autosomal recessive mode of inheritance. Only two homozygous VRK1 pathogenic variants were reported to date in PCH. The first is a nonsense variant (c.1072C>T; p.Arg358*) that was identified in a large PCH1 consanguineous family of Ashkenazi Jewish ancestry. In this family, the clinical features were mild and patients lived into their early teens (Renbaum et al. 2009. PubMed ID: 19646678). The second pathogenic variant is of the missense type (c.397C>T, p.Arg133Cys), and was reported in one single patient (Najmabadi et al. 2011. PubMed ID: 21937992). Detailed clinical features are unavailable for this patient.

No pathogenic large deletions or regulatory variants have been reported in the VRK1 gene.

The VRK1 gene encodes vaccinia-related kinase 1, a serine-threonine protein kinase, which is hypothesized to play a coordinator role in the process of cell division (Valbuena et al. 2008. PubMed ID: 18286197).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the VRK1 gene appear to be a rare cause of PCH (Renbaum et al. 2009. PubMed ID: 19646678).

Thus far, no pathogenic gross deletions or duplications have been reported involving the VRK1 gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the VRK1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with a combination of pontocerebellar hypoplasia and infantile spinal muscular atrophy, a family history consistent with autosomal recessive mode of inheritance, and no pathogenic variants in the EXOSC3 gene. Family members of patients who have known VRK1 pathogenic variants are also candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in VRK1.

Gene

Official Gene Symbol OMIM ID
VRK1 602168
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Pontocerebellar Hypoplasia Type 1 AR 607596

Related Test

Name
Pontocerebellar Hypoplasia Panel

Citations

  • Barth. 1993. PubMed ID: 8147499
  • Burglen et al. 2012. PubMed ID: 22452838
  • Human Gene Mutation Database (Bio-base).
  • Najmabadi et al. 2011. PubMed ID: 21937992
  • Namavar et al. 2011. PubMed ID: 21368912
  • Norman. 1961. PubMed ID: 13729575
  • Renbaum et al. 2009. PubMed ID: 19646678
  • Rudnik-Sch├Âneborn et al. 2003. PubMed ID: 12548734
  • Samanta and Willis. 2016. PubMed ID: 27570394
  • Valbuena et al. 2008. PubMed ID: 18286197

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

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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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