Generalized Arterial Calcification of Infancy and Pseudoxanthoma Elasticum (PXE) via the ABCC6 Gene
Summary and Pricing 
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 | |
---|---|---|---|---|---|
7857 | ABCC6 | 81479 | 81479,81479 | $1890 | 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.
Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).
Click here for costs to reflex to whole PGxome.
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
Generalized arterial calcification of infancy (also referred as Idiopathic infantile arterial calcification) is a rare infantile onset calcification of the internal elastic lamina of medium and large arteries and arterial stenosis due to myointimal proliferation (Rutsch et al. 2003. PubMedID: 12881724; Chong and Hutchins. 2008. PubMed ID: 17990935). The major early clinical features include fetal distress, heart failure, hydramnios, respiratory distress, hydrops fetalis, fetal edema, cyanosis, effusions in the pleural, peritoneal, pericardial spaces and cardiomegaly. The major late clinical features are respiratory distress, cyanosis, feeding difficulties, and heart failure (Chong and Hutchins. 2008. PubMed ID: 17990935). Without proper medical management, ~60% of the patients die from cardiovascular complications or renal artery stenosis within the first 6 months of life (Rutsch et al. 2001. PubMed ID: 11159191; Rutsch et al. 2008. PubMed ID: 20016754; Ferreira et al. 2014. PubMed ID: 25392903).
Pseudoxanthoma elasticum (PEX) is a progressive condition characterized by ectopic mineralization in elastic fibers of connective tissues mainly in skin, retina, and blood vessels. Patients may present yellowish papules in skin, progressive visual loss and cardiovascular symptoms. Cardiovascular symptoms include rupture of blood vessels particularly within the gastrointestinal tract, and early myocardial infarction (Bergen et al. 2000. PubMed ID: 10835643; Ringpfeil et al. 2000. PubMed ID: 10811882). The estimated disease prevalence is between 1/25,000 and 1/50,000 in general populations and the estimated carrier frequency is one in 111 to one in 80 individuals (Legrand et al. 2017. PubMed ID: 28102862).
Genetics
Generalized arterial calcification of infancy is inherited in an autosomal recessive manner caused by pathogenic variants in the ENPP1 and ABCC6 genes.
The ABCC6 protein (ATP-binding cassette subfamily C member 6) coded by ABCC6 is a member of the ATP-binding cassette (ABC) protein family and serves serves as an efflux transporter and regulates plasmatic inorganic pyrophosphate (Jansen et al. 2014. PubMed ID: 24969777).
ABCC6 is the major gene involved in autosomal recessive pseudoxanthoma elasticum (Legrand et al. 2017. PubMed ID: 28102862). To date, ~350 unique pathogenic variants have been reported. They include miseense (~53%), truncating (~28%), splicing (~7%), large deletion and gross rearrangements (~11%) (Human Gene Mutation Database). A nonsense variant c.3421C>T, p.Arg1141* in exon 24 was found in 25% of cases from all ethnic backgrounds, and a large deletion involving exons 23 to 29 was found in 28% of American patients of European descent (Legrand et al. 2017. PubMed ID: 28102862).
Pathogenic ABCC6 variants have also been reported in patients with autosomal recessive generalized arterial calcification of infancy (Nitschke et al. 2012. PubMed ID: 22209248) and found in a few families with debatable autosomal dominant inheritance pattern of Pseudoxanthoma elasticum, forme fruste (Bergen et al. 2000. PubMed ID: 10835643; Bergen. 2006. PubMed ID: 16541094). No genotype-phenotype correlations have been established.
Clinical Sensitivity - Sequencing with CNV PG-Select
In one study, pathogenic variants in the ABCC6 gene were reported in 88% of patients with clinically diagnosed Pseudoxanthoma elasticum (Legrand et al. 2017. PubMed ID: 28102862). A nonsense variant c.3421C>T, p.Arg1141Ter in exon 24 was found in 25% cases from all ethnic backgrounds, and a large deletion involving exons 23 to 29 was found in 28% of American patients of European descent (Legrand et al. 2017. PubMed ID: 28102862).
Testing Strategy
This test provides full coverage of all coding exons of the ABCC6 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing. This test also detects the ABCC6 c.1780-29T>A and c.2248-12_2248-11del variants.
Due to the homologous sequence at the region of exons 1 to exon 9 of ABCC6, we utilize a long-range PCR strategy to specifically amplify and sequence these exons, which is able to overcome the limitation of current short-read NGS technology in dealing with this type of homologous sequence (Mandelker et al. 2016. PubMed ID: 27228465).
Indications for Test
Candidates for this test are patients with a clinical suspicion of with autosomal dominant pseudoxanthoma elasticum forme fruste, and autosomal recessive generalized arterial calcification of infancy/pseudoxanthoma elasticum. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ABCC6.
Candidates for this test are patients with a clinical suspicion of with autosomal dominant pseudoxanthoma elasticum forme fruste, and autosomal recessive generalized arterial calcification of infancy/pseudoxanthoma elasticum. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ABCC6.
Gene
Official Gene Symbol | OMIM ID |
---|---|
ABCC6 | 603234 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Diseases
Name | Inheritance | OMIM ID |
---|---|---|
Arterial Calcification, Generalized, of Infancy, 2 | AR | 614473 |
Pseudoxanthoma Elasticum | AR | 264800 |
Pseudoxanthoma Elasticum, Forme Fruste | AD | 177850 |
Related Test
Name |
---|
Generalized Arterial Calcification of Infancy and Pseudoxanthoma Elasticum Panel |
Citations 
- Bergen et al. 2000. PubMed ID: 10835643
- Bergen. 2006. PubMed ID: 16541094
- Chong and Hutchins. 2008. PubMed ID: 17990935
- Ferreira et al. 2014. PubMed ID: 25392903
- Human Gene Mutation Database (Bio-base).
- Jansen et al. 2014. PubMed ID: 24969777
- Legrand et al. 2017. PubMed ID: 28102862
- Mandelker et al. 2016. PubMed ID: 27228465
- Nitschke et al. 2012. PubMed ID: 22209248
- Ringpfeil et al. 2000. PubMed ID: 10811882
- Rutsch et al. 2001. PubMed ID: 11159191
- Rutsch et al. 2003. PubMed ID: 12881724
- Rutsch et al. 2008. PubMed ID: 20016754
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
ORDER OPTIONS
View Ordering Instructions1) 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.