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Chondrodysplasia Punctata 1, X-Linked Recessive (CDPX1) via the ARSL/ARSE Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9935 ARSL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9935ARSL81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Juan Dong, PhD, FACMG

Clinical Features and Genetics

Clinical Features

X-linked recessive chondrodysplasia punctata 1 (CDPX1, OMIM#302950) is characterized by abnormal cartilage and bone development, including chondrodysplasia punctata (stippled epiphyses) especially in the hands and feet, short stature, brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. Although most affected males have minimal morbidity and skeletal findings that improve by adulthood, some have significant medical problems including respiratory compromise, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and abnormal cognitive development (Braverman et al. GeneReviews. 2008).

Genetics

CDPX1 is inherited in an X-linked recessive manner. This condition is caused by a deficiency of the Golgi enzyme arylsulfatase E encoded by the ARSL/ARSE gene. ARSL is located in Xp22.3, close to the pseudoautosomal boundary within a cluster of evolutionarily related sulfatase genes, which encodes steroid sulfatase. These genes escape X-inactivation and have a pseudogene on the Y chromosome (Sardiello et al. Hum Mol Genet 14:3203–3217, 2005). The majority of disease-associated variants in the ARSL gene are missense and nonsense variants, although small insertions as well as gross deletions have been reported (Nino et al. Am J Med Genet 146A:997–1008, 2008). In approximately 25% of individuals with features of CDPX1, routine karyotype analysis reveals Xp deletions or rearrangements that include ARSL (Braverman et al. GeneReviews 2008; Ballabio & Andria Hum Mol Genet 1:221-227, 1992).

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing of ARSL is predicted to detect disease variants in up to 75% of males who meet clinical diagnostic criteria (Franco et al. Cell 81:15-25, 1995; Sheffield et al. J Med Genet 35:1004–1008, 1998; Brunetti-Pierri et al. Am J Med Genet 117A:164-168, 2003; Garnier et al. Eur J Pediatr 166:327–31, 2007; Nino et al. Am J Med Genet 146A:997–1008, 2008). The failure to achieve higher variant detection rates could reflect the inclusion of phenocopies (e.g. warfarin embryopathy, maternal vitamin K deficiency), genetic heterogeneity, or variants in regions of ARSL that were not sequenced.  Note: ARSLgene deletions are suspected in males based on failed amplification of either the entire gene or specific exons. Those large deletions would typically not be detected in female carriers by sequence analysis.

Testing Strategy

This test provides full coverage of all coding exons of the ARSL 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with clinical and radiographic features consistent with CDPX1 and family members of patients who have known ARSL variants.

Gene

Official Gene Symbol OMIM ID
ARSL 300180
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Chondrodysplasia Punctata 1, X-Linked Recessive 302950

Citations

  • Ballabio, A., Andria, G. (1992). "Deletions and translocations involving the distal short arm of the human X chromosome: review and hypotheses." Hum Mol Genet 1(4): 221-7. PubMed ID: 1303191
  • Braverman, Nancy E (2008). "Chondrodysplasia Punctata 1, X-Linked Recessive."
  • Braverman, Nancy E (2008). "Chondrodysplasia Punctata 1, X-Linked Recessive."
  • Brunetti-Pierri, N., et.al. (2003). "X-linked recessive chondrodysplasia punctata: spectrum of arylsulfatase E gene mutations and expanded clinical variability." Am J Med Genet A 117A(2): 164-8. PubMed ID: 12567415
  • Franco, B., et.al. (1995). "A cluster of sulfatase genes on Xp22.3: mutations in chondrodysplasia punctata (CDPX) and implications for warfarin embryopathy." Cell 81(1): 15-25. PubMed ID: 7720070
  • Garnier, A., et.al. (2007). "Brachytelephalangic chondrodysplasia punctata with severe spinal cord compression: report of four new cases." Eur J Pediatr 166(4): 327-31. PubMed ID: 16937129
  • Nino, M., et.al. (2008). "Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata." Am J Med Genet A 146A(8): 997-1008. PubMed ID: 18348268
  • Nino, M., et.al. (2008). "Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata." Am J Med Genet A 146A(8): 997-1008. PubMed ID: 18348268
  • Sardiello, M., et.al. (2005). "Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship." Hum Mol Genet 14(21): 3203-17. PubMed ID: 16174644
  • Sheffield, L. J., et.al. (1998). "Segregation of mutations in arylsulphatase E and correlation with the clinical presentation of chondrodysplasia punctata." J Med Genet 35(12): 1004-8. PubMed ID: 9863597

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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