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Congenital Dyserythropoietic Anemia Type II via the SEC23B 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
11653 SEC23B 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11653SEC23B81479 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

  • Luke Drury, PhD

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: type I (CDAN1), type II (SEC23B), type III (sporadic with unknown genetic etiology), and type IV (KLF1 and GATA1) (Iolascon et al. 2012). Overlapping symptoms include jaundice, ineffective erythropoiesis, gall stone formation 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. 2010).

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 II CDA is rarely associated with skeletal abnormalities as seen more commonly in individuals with type I CDA (Bianchi et al. 2009).

Genetics

Type II CDA is inherited in an autosomal recessive manner through mutations in the SEC23B gene. Missense, nonsense, splice site, and small insertion/deletion mutations account for 52%, 20%, 13%, and 13% of causative variants and occur throughout the coding region of the SEC23B gene (Russo et al. 2010; Bianchi et al. 2009; Iolascon et al. 2010). A sole case has reported a deletion of exons 3 and 4 (Schwartz et al. 2009). Compound heterozygosity for missense and nonsense mutations tends to correlate with more severe clinical presentations (Iolascon et al. 2010). Homozygosity or compound heterozygosity for null mutations has never been found and is thought to be lethal. Complete deletion of the Sec23b gene in mice results in death shortly after birth due to degeneration of secretory tissues (Tao et al. 2012). The SEC23B gene encodes a component of the COPII (coat protein) complex responsible for accumulation of secretory cargo, deformation of the membrane, and transport of cargo from the endoplasmic reticulum to the Golgi apparatus. Defects in this protein are predicted to result in hypoglycosylation of erythrocyte membrane proteins which contributes to disease onset in type II CDA (Schwartz et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

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 mutation in the SEC23B gene is 95% as gross deletions have only been reported in a single case (Schwarz et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the SEC23B 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 II CDA indicates bi- and multi-nuclearity of mature erythroblasts by light microscopy and peripheral cisternae beneath the plasma membrane by electron microscopy (Iolascon et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SEC23B.

Gene

Official Gene Symbol OMIM ID
SEC23B 610512
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dyserythropoietic Anemia, Congenital, Type II AR 224100

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
  • 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
  • Iolascon A, Russo R, Esposito MR, Asci R, Piscopo C, Perrotta S, Feneant-Thibault M, Garcon L, Delaunay J. 2010. Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship. Haematologica 95: 708–715. PubMed ID: 20015893
  • 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
  • Russo R, Esposito MR, Asci R, Gambale A, Perrotta S, Ramenghi U, Forni GL, Uygun V, Delaunay J, Iolascon A. 2010. Mutational spectrum in congenital dyserythropoietic anemia type II: Identification of 19 novel variants in SEC23B gene. American Journal of Hematology 85: 915–920. PubMed ID: 20941788
  • 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
  • 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.
  • 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.
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