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Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) Syndrome via the VPS33B 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
15413 VPS33B 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15413VPS33B81479 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

18 days on average for standard orders or 13 days 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

  • Chansonette Badduke, PhD

Clinical Features and Genetics

Clinical Features

Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC syndrome; OMIM #208085) 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. J Pediatrics 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 (OMIM #608552) 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. 2010). Nonsense and splice site variants represent the most common forms of VPS33B variant although missense and frame-shifting variants are also reported. Variants in the VIPAR 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. Nature Genet 42:303-312, 2010).

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 also. Twenty-eight of 35 ARC syndrome families in one study were found to have two VPS33B variants (Gissen et al. 2006).

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 VPS33B 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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in VPS33B.

Gene

Official Gene Symbol OMIM ID
VPS33B 608552
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Cullinane, A. R., et.al. (2010). PubMed ID: 20190753
  • Di Rocco, M., et.al. (1990). PubMed ID: 2248291
  • Di Rocco, M., et.al. (1995). PubMed ID: 8529684
  • Gissen, P., et.al. (2004). PubMed ID: 15052268
  • Gissen, P., et.al. (2006). PubMed ID: 16896922
  • Horslen, S. P., et.al. (1994). PubMed ID: 8151641
  • Nezelof, C., et.al. (1979). PubMed ID: 762621
  • Saraiva, J. M., et.al. (1990). PubMed ID: 2231211
  • Taha, D., et.al. (2007). 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


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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