Pontocerebellar Hypoplasia via the VRK1 Gene
Summary and Pricing ![](img/next-arrow.png)
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
7379 | VRK1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
Clinical Features and Genetics ![](img/next-arrow.png)
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.
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 ![](img/next-arrow.png)
- 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-Schöneborn et al. 2003. PubMed ID: 12548734
- Samanta and Willis. 2016. PubMed ID: 27570394
- Valbuena et al. 2008. PubMed ID: 18286197
Ordering/Specimens ![](img/next-arrow.png)
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.