Spinal Muscular Atrophy, Autosomal Dominant, Adult-Onset and Amyotrophic Lateral Sclerosis-8 via the VAPB Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 8927 | VAPB | 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
Clinical Features
A variant of amyotrophic lateral sclerosis (ALS), termed ALS8 (OMIM 608627), and mild, late-onset spinal muscular atrophy (OMIM 182980) have been attributed to a variant in vesicle associated protein B, coded by VAPB (OMIM 605704). ALS8 demonstrates earlier onset and slower clinical course than classic ALS (Nishimura et al. J Med Genet 41:315-320, 2004). The mean age of disease onset was 38 years in a large Brazilian kindred, and notable initial symptoms include painful cramps, fasciculation, tremor, weakness, and fatigue (Nishimura et al., 2004). Postural tremor, which was stable over time, was also an early sign. Lower motor neuron involvement was a universal symptom, and all four limbs were affected. Serum CK was normal or slightly elevated and muscle biopsies demonstrated a neurogenic pattern (Nishimura et al. 2004). In other family members, clinical symptoms resemble a late-onset, slowly progressive spinal muscular atrophy (Nishimura et al. Am J Hum Genet 75:822-831, 2004).
Genetics
Disorders associated with VAPB demonstrate autosomal dominant inheritance. A VAPB missense variant in exon 2 has been found to segregate with disease in a White Brazilian family of Portuguese decent (Nishimura at al., J Med Genet 41:315-320, 2004; Nishimura at al. Hum Genet 118:499-500, 2005). The disorder is completely penetrant within the reported family, although variability in clinical symptoms suggests the effect of modifier genes.
Clinical Sensitivity - Sequencing with CNV PG-Select
Variants in VAPB are a rare cause of disease. Thus far the Portuguese p.Pro56Ser variant is the only pathogenic variant reported. Evidence suggests that VAPB is not significantly associated with sporadic ALS (Kirby et al. Neurology 68:1951-1953, 2007).
Testing Strategy
This test provides full coverage of all coding exons of the VAPB gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Specific clinical signs observed in affected members of the Brazilian family include lower motor neuron symptoms with involvement in all four limbs, bulbar involvement, postural tremor, and painful cramping (Nishimura et al. J Med Genet 41:315-320, 2004).
Specific clinical signs observed in affected members of the Brazilian family include lower motor neuron symptoms with involvement in all four limbs, bulbar involvement, postural tremor, and painful cramping (Nishimura et al. J Med Genet 41:315-320, 2004).
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| VAPB | 605704 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Adult Proximal Spinal Muscular Atrophy, Autosomal Dominant | AD | 182980 |
| Amyotrophic Lateral Sclerosis Type 8 | AD | 608627 |
Citations
- Kirby, J., et.al. (2007). "Mutations in VAPB are not associated with sporadic ALS." Neurology 68(22): 1951-3. PubMed ID: 17536055
- Nishimura, A. L., et.al. (2004). "A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis." Am J Hum Genet 75(5): 822-31. PubMed ID: 15372378
- Nishimura, A. L., et.al. (2004). "A novel locus for late onset amyotrophic lateral sclerosis/motor neurone disease variant at 20q13." J Med Genet 41(4): 315-20. PubMed ID: 15060112
- Nishimura, A. L., et.al. (2005). "A common founder for amyotrophic lateral sclerosis type 8 (ALS8) in the Brazilian population." Hum Genet 118(3-4): 499-500. PubMed ID: 16187141
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
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
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ORDER OPTIONS
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