Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) Syndrome via the VIPAS39 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 | |
|---|---|---|---|---|---|
| 15411 | VIPAS39 | 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
Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC syndrome; OMIM #613404) is a multisystem disorder with features of arthrogryposis multiplex congenita, renal tubular hypoplasia, and cholestatic liver disease (Di Rocco et al. Am J Med Genet 37:237-240, 1990; Di Rocco et al. Eur J Pediatr 154:835-839, 1995). Life-threatening complications of malabsorption secondary to cholestatic jaundice appear shortly after birth (Nezelof et al. J Pediatrics 94:258-260, 1979). The majority of patients succumb in several weeks to several months of life (Gissen et al. Hum Genet 120:396-409, 2006). Renal disease involves renal tubular cell degeneration and nephrocalcinosis (Saraiva et al. Clin Lab Obs 117:761-763, 1990). Liver histology in ARC syndrome has been reviewed (Horslen et el. J Med Genet 31:62-64, 1994). Bile duct hypoplasia and low gamma glutamyl transpeptidase activity are documented (Gissen et al. 2006). Other clinical findings described in a cohort of 62 ARC syndrome patients included failure to thrive (100%) and structural cardiac defects (10%) (Gissen et al. 2006). The same study found a high rate of life-threatening hemorrhagic events during diagnostic organ biopsy procedures. Severe osteopenia with congenital fractures has been reported in one ARC syndrome patient (Taha et al. Am J Med Genet 143A:2835-2837, 2007).
Genetics
ARC syndrome is inherited as an autosomal recessive disorder. VPS33B was found to be a causative gene for ARC syndrome (Gissen et al. Nat Genet 36:400-404, 2004), and is thought to account for approximately 75% of cases (Cullinane et al. Nature Genet 42:303-312, 2010). Variants in the VIPAS39 gene, which encodes a ‘VPS33B-interacting protein’, have been found in all cases of classic ARC syndrome when VPS33B variants were not identified (Cullinane et al. 2010). All reported VIPAS39 variants result in premature protein termination.
Clinical Sensitivity - Sequencing with CNV PG-Select
Analytical sensitivity should be high because all variants reported to date are detectable by direct sequence analysis of genomic DNA. Clinical sensitivity appears to be high in patients with classic symptoms and who test negative for VPS33B variants.
Testing Strategy
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.
This test provides full coverage of all coding exons of the VIPAS39 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with the triad of symptoms of arthrogryposis multiplex congenita, renal dysfunction, and cholestasis and who have negative test results for the VPS33B gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in VIPAS39.
Individuals with the triad of symptoms of arthrogryposis multiplex congenita, renal dysfunction, and cholestasis and who have negative test results for the VPS33B gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in VIPAS39.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| VIPAS39 | 613401 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Arthrogryposis, Renal Dysfunction, And Cholestasis 2 | AR | 613404 |
Citations
- Cullinane, A. R., et.al. (2010). "Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization." Nat Genet 42(4): 303-12. PubMed ID: 20190753
- Di Rocco, M., et.al. (1990). "Arthrogryposis, cholestatic pigmentary liver disease and renal dysfunction: report of a second family." Am J Med Genet 37(2): 237-40. PubMed ID: 2248291
- Di Rocco, M., et.al. (1995). "Arthrogryposis, renal dysfunction and cholestasis syndrome: report of five patients from three Italian families." Eur J Pediatr 154(10): 835-9. PubMed ID: 8529684
- Gissen, P., et.al. (2004). "Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome." Nat Genet 36(4): 400-4. PubMed ID: 15052268
- Gissen, P., et.al. (2006). "Clinical and molecular genetic features of ARC syndrome." Hum Genet 120(3): 396-409. PubMed ID: 16896922
- Horslen, S. P., et.al. (1994). "Liver histology in the arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC) syndrome: report of three new cases and review." J Med Genet 31(1): 62-4. PubMed ID: 8151641
- Nezelof, C., et.al. (1979). "A lethal familial syndrome associating arthrogryposis multiplex congenita, renal dysfunction, and a cholestatic and pigmentary liver disease." J Pediatr 94(2): 258-60. PubMed ID: 762621
- Saraiva, J. M., et.al. (1990). "Arthrogryposis multiplex congenita with renal and hepatic abnormalities in a female infant." J Pediatr 117(5): 761-3. PubMed ID: 2231211
- Taha, D., et.al. (2007). "A novel VPS33B mutation in an ARC syndrome patient presenting with osteopenia and fractures at birth." Am J Med Genet A 143A(23): 2835-7. PubMed ID: 17994566
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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