Congenital Dyserythropoietic Anemia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10193 CDAN1 81479,81479 Order Options and Pricing
CDIN1 81479,81479
GATA1 81479,81479
KLF1 81479,81479
SEC23B 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10193Genes x (5)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Congenital Dyserythropoietic Anemia (CDA) is a disorder that results in defective 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).

Type I CDA is characterized by moderate to severe anemia through mutations in either the CDAN1 or CDIN1/C15ORF41 genes and is the second most prevalent form. Diagnosis is typically during childhood, but can be made before birth in severe cases. Type II CDA, the most common form with about 450 cases worldwide, is characterized by mild to severe anemia through mutations in the SEC23B gene. Affected individuals are diagnosed in adolescence and are at higher risk for formation of gallstones. Type III CDA is primarily a sporadic form of disease with unknown genetic etiology. Type IV CDA has been reported in ~10 cases and inherited in an autosomal dominant manner through mutations in either the KLF1 or GATA1 genes. Different forms of CDA may be distinguished through sequencing analysis of the causative genes or bone marrow erythroblast morphology (Iolascon et al. 2012).

Genetics

CDA is inherited in an autosomal recessive manner through mutations in the CDAN1 (type I), CDIN1 (type I), and SEC23B (type II) genes. Missense mutations are predominant as there have been no patients documented that are homozygous for null mutations in either the CDAN1 or SEC23B genes. Consistent with this notion, Cdan1 knockout mice die in utero prior to erythropoiesis onset (Renella et al. 2011; Tao et al. 2012). KLF1 and GATA1 mutations are associated with autosomal dominant inherited and X-linked recessive forms of CDA type IV, respectively (Iolascon et al. 2012). See individual test descriptions for additional information on the molecular biology of each gene.

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the CDAN1 gene were identified in 90% of type I CDA cases (Tamary and Dgany 2009). In patients with type II CDA, mutations in the SEC23B gene were identified in 12 of 13 and 16 of 16 unrelated individuals (Bianchi et al. 2009; Punzo et al. 2011). Analytical sensitivity for detection of mutations in the CDAN1 and SEC23B genes is >95% as gross deletions have only been reported in single cases of type I and type II CDA (Heimpel et al. 2006; Schwarz et al. 2009). Analytical sensitivity for the CDIN1, GATA1 and KLF1 genes should be high because all mutations reported to date are detectable by this method. Clinical sensitivity for CDIN1, GATA1 and KLF1 is unknown due to the small number of patients reported to date.

No gross deletions or duplications have been reported in GATA1 to date (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates have clinical features consistent with CDA including jaundice, anemia, splenomegaly, gallstones, and secondary hemochromatosis. Other pathological findings for CDA include aniso-poikilocytosis and basophilic stippling on peripheral blood smears, bone marrow morphology indicating dyserythropoiesis, and moderate anemia (mean hemoglobin levels 85±6 g/L) (Iolascon et al. 2012; Tamary and Dgany 2009).

Genes

Official Gene Symbol OMIM ID
CDAN1 607465
CDIN1 615626
GATA1 305371
KLF1 600599
SEC23B 610512
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Bianchi P, Fermo E, Vercellati C, Boschetti C, Barcellini W, Iurlo A, Marcello AP, Righetti PG, Zanella A. 2009. Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Human Mutation 30: 1292–1298. PubMed ID: 19621418
  • 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
  • Human Gene Mutation Database (Bio-base).
  • 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
  • Punzo F, Bertoli-Avella AM, Scianguetta S, Della Ragione F, Casale M, Ronzoni L, Cappellini MD, Forni G, Oostra BA, Perrotta S. 2011. Congenital Dyserythropoietic Anemia Type II: molecular analysis and expression of the SEC23B Gene. Orphanet J Rare Dis 6: 89. PubMed ID: 22208203
  • 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
  • Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W, Paw BH, Hopfner K-P, Holzmann K, Russo R, Esposito MR, Spano D, De Falco L, Heinrich K, Joggerst B, Rojewski MT, Perrotta S, Denecke J, Pannicke U, Delaunay J, Pepperkok R, Heimpel H. 2009. Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nature Genetics 41: 936–940. PubMed ID: 19561605
  • 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
  • Tao J, Zhu M, Wang H, Afelik S, Vasievich MP, Chen X-W, Zhu G, Jensen J, Ginsburg D, Zhang B. 2012. SEC23B is required for the maintenance of murine professional secretory tissues. Proceedings of the National Academy of Sciences 109: E2001–E2009. PubMed ID: 22745161

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.

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

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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.

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