Congenital Dyserythropoietic Anemia Type I via the CDAN1 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
11161 CDAN1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11161CDAN181479 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

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Congenital Dyserythropoietic Anemia (CDA) is a disorder that affects erythropoiesis leading to anemia. There are four types of CDA caused by mutations in different genes. Overlapping symptoms include jaundice and splenomegaly. Chronic anemia can cause secondary hemochromatosis and lead to tissue damage and organ failure in severe cases. Genetics is helpful in differential diagnosis of CDA types and from other broader syndromes where CDA also occurs including Majeed Syndrome, Mevalonate Kinase Deficiency, and exocrine pancreatic insufficiency (Iolascon et al. 2012; Tamary and Dgany 2009).

Type I CDA is the second most prevalent form of the disease and is characterized by moderate to severe anemia through mutations in either the CDAN1 or C15ORF41 genes. Diagnosis is typically during childhood, but can be made before birth in severe cases. Type I CDA is occasionally associated with skeletal abnormalities in the hands and feet, nail hypoplasia, and scoliosis (Tamary and Dgany 2009).

Genetics

Type I CDA is inherited in an autosomal recessive manner primarily through mutations in the CDAN1 gene. However, mutations in the C15ORF41 gene have been described in three families with type I CDA (Babbs et al. 2013). There is no clear phenotype-genotype correlation as marked clinical variability is seen among patients with the same pathogenic variants. Missense, frameshift, nonsense, splice site and small insertion/deletion mutations account for 60%, 15%, 10%, 10%, and 5% of the causative variants in the CDAN1 gene (Dgany et al. 2002; Tamary and Dgany et al. 2009; Heimpel et al. 2006). A sole report has identified a deletion encompassing exon 28 (Heimpel et al. 2006). No patients are documented being homozygous for null mutations in the CDAN1 gene. Consistent with this notion, Cdan1 knockout mice die in utero prior to erythropoiesis onset (Renella et al. 2011). The majority of the causative mutations are in exons 14 and 24 with other mutations occurring in the latter half of the coding region (Dgany et al. 2002). In 28% of type I CDA individuals, only one pathogenic variant in the CDAN1 gene is identified (Iolascon et al. 2012). The CDAN1 gene encodes the protein codanin-1 which modulates S-phase during DNA replication through regulation of a chromatin bound histone chaperone, Asf1 (Ask et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the CDAN1 gene were identified in 90% of type I CDA cases (Tamary and Dgany 2009). Analytical sensitivity for detection of mutation in the CDAN1 gene is probably >95% as gross deletions have only been reported in a sole case (Heimpel et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the CDAN1 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 have clinical features consistent with CDA including jaundice, anemia, splenomegaly, gallstones, and secondary hemochromatosis. Bone marrow morphology analysis of patients with type I CDA indicates abnormal chromatin bridging by light microscopy and spongy heterochromatin with invagination of the cytoplasm into the nucleus by electron microscopy (Iolascon et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CDAN1.

Gene

Official Gene Symbol OMIM ID
CDAN1 607465
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dyserythropoietic Anemia, Congenital, Type Ia AR 224120

Citations

  • Ask K, Jasencakova Z, Menard P, Feng Y, Almouzni G, Groth A. 2012. Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply. The EMBO journal 31: 2013–2023. PubMed ID: 22407294
  • Babbs C, Roberts NA, Sanchez-Pulido L, McGowan SJ, Ahmed MR, Brown JM, Sabry MA, WGS500 Consortium, Bentley DR, McVean GA, Donnelly P, Gileadi O, et al. 2013. Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. Haematologica 98: 1383–1387. PubMed ID: 23716552
  • Dgany O, Avidan N, Delaunay J, Krasnov T, Shalmon L, Shalev H, Eidelitz-Markus T, Kapelushnik J, Cattan D, Pariente A, others. 2002. Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. The American Journal of Human Genetics 71: 1467–1474. PubMed ID: 12434312
  • Heimpel H, Schwarz K, Ebnöther M, Goede JS, Heydrich D, Kamp T, Plaumann L, Rath B, Roessler J, Schildknecht O, Schmid M, Wuillemin W, Einsiedler B, Leichtle R, Tamary H, Kohne E. 2006. Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation. Blood 107: 334–340. PubMed ID: 16141353
  • Iolascon A, Esposito MR, Russo R. 2012. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. Haematologica 97: 1786–1794. PubMed ID: 23940284
  • Renella R, Roberts NA, Brown JM, Gobbi M De, Bird LE, Hassanali T, Sharpe JA, Sloane-Stanley J, Ferguson DJ, Cordell J, others. 2011. Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts. Blood 117: 6928–6938. PubMed ID: 21364188
  • Tamary H, Dgany O. 2009. Congenital Dyserythropoietic Anemia Type I. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301759

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×