Conradi-Hunermann syndrome via the EBP 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
8935 EBP 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8935EBP81479 81479(x2) $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

Chondrodysplasia punctata (CDP) is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. X-linked dominant CDP (CDPX2), also known as Conradi-Hunermann syndrome (OMIM #302960), is the best characterized form. CDPX2 patients display skin defects including linear or whorled atrophic and pigmentary lesions, striated hyperkeratosis, coarse lusterless hair and alopecia, cataracts, and skeletal abnormalities including short stature, rhizomelic shortening of the limbs, epiphyseal stippling, and craniofacial defects (Derry et al. Nature Genet. 22: 286-290, 1999).

Genetics

Conradi-Hunermann syndrome/CDPX2 is inherited in an X-linked dominant manner. Incomplete penetrance and variable expressivity have been noted (Ausavarat et al. Eur. J. Derm. 18: 391-393, 2008), which may reflect different patterns of X-inactivation. CDPX2 was presumed to cause male lethality prenatally; however, hemizygous males with an EBP variant have been reported (Traupe et al. Am. J. Med. Genet. 85:324-329, 1999; Metzenberg et al. Am. J. Hum. Genet. 65:A480, 1999; Milunsky et al. Am. J. Med. Genet., 116A:249-254, 2003). These reported males have various features, ranging from mildly affected to typical CDPX2. EBP is the only gene currently known to be associated with CDPX2. EBP encodes the delta(8)-delta(7) sterol isomerase emopamil binding protein, an enzyme involved in postsqualene cholesterol biosynthesis. EBP is an integral membrane protein of the endoplasmic reticulum. It is similar to sigma receptors and may be a member of a superfamily of high affinity drug-binding proteins in the endoplasmic reticulum of different tissues. It has four putative transmembrane segments and contains two conserved glutamate residues, which may be involved in the transport of cationic amphiphilics. Another prominent feature of this protein is its high content of aromatic amino acid residues (>23%) in its transmembrane segments. These aromatic amino acid residues have been suggested to be involved in the drug transport by the P-glycoprotein (Hanner et al. J. Biol. Chem. 270:7551-7557, 1995).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect disease variants in ~90% of affected individuals with CDPX2 (Derry et al. Nature Genet. 22:286-290, 1999; Braverman et al. Nature Genet. 22:291-294, 1999, Ikegawa et al. Am. J. Med. Genet. 94:300-305, 2000; Herman et al. Genet. Med. 4:434-438, 2002; Has et al. Hum. Mol. Genet. 9:1951-1955, 2000).

Testing Strategy

This test provides full coverage of all coding exons of the EBP 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/radiographic features or an abnormal sterol profile consistent with CDPX2, and family members of patients who have known EBP variants.

Gene

Official Gene Symbol OMIM ID
EBP 300205
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Chondrodysplasia Punctata 2 X-Linked Dominant XL 302960

Citations

  • Ausavarat, S., et.al. (2008). "Two novel EBP mutations in Conradi-Hunermann-Happle syndrome." Eur J Dermatol 18(4): 391-3. PubMed ID: 18573709
  • Braverman, N., et.al. (1999). "Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase cause X-linked dominant Conradi-Hunermann syndrome." Nat Genet 22(3): 291-4. PubMed ID: 10391219
  • Derry, J. M., et.al. (1999). "Mutations in a delta 8-delta 7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. jderry@immunex.com." Nat Genet 22(3): 286-90. PubMed ID: 10391218
  • Hanner, M., et.al. (1995). "Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression." J Biol Chem 270(13): 7551-7. PubMed ID: 7706302
  • Has, C., et.al. (2000). "The Conradi-Hunermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism." Hum Mol Genet 9(13): 1951-5. PubMed ID: 10942423
  • Herman, G. E., et.al. (2002). "Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome)." Genet Med 4(6): 434-8. PubMed ID: 12509714
  • Ikegawa, S., et.al. (2000). "Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata." Am J Med Genet 94(4): 300-5. PubMed ID: 11038443
  • Metzenberg, A. B. (1999). "The American Society of Human Genetics 49th annual meeting. San Francisco, California, USA. October 19-23, 1999. Abstracts Mutations in chondrodysplasia punctata, X-linked dominant type (CDPX2)."." Am J Hum Genet 65(4 Suppl): A480." PubMed ID: 10546578
  • Milunsky, J. M., et.al. (2003). "Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP." Am J Med Genet A 116A(3): 249-54. PubMed ID: 12503101
  • Traupe, H. (1999). "Functional X-chromosomal mosaicism of the skin: Rudolf Happle and the lines of Alfred Blaschko." Am J Med Genet 85(4): 324-9. PubMed ID: 10398252

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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