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 ALAS2 81479,81479 Order Options and Pricing
CAD 81479,81479
CDAN1 81479,81479
CDIN1 81479,81479
GATA1 81479,81479
KIF23 81479,81479
KLF1 81479,81479
LPIN2 81479,81479
SEC23B 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10193Genes x (9)81479 81479(x18) $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 Custom Panel tool.

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).

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

Clinical Features and Genetics

Clinical Features

Congenital dyserythropoietic anemia (CDA) is a disorder that results in defective erythropoiesis leading to anemia. There are four subgroups of CDAs: type I, type II, type III, and type IV. Type I accounts for ~12% of cases with onset in childhood. Symptoms include moderate to severe anemia, jaundice, hepatosplenomegaly, and in ~10% of cases, distal limb anomalies. Type II is the most common accounting for ~75% of CDA cases and over 300 cases worldwide. Onset occurs in adolescence or early adulthood with symptoms including mild to severe anemia, jaundice, hepatosplenomegaly, and gall stones. Type III patients present with mild anemia and jaundice, but splenomegaly is usually absent. Type IV CDA is a subgroup of disorders related to transcription factor mutations including two X-linked dominant forms due to pathogenic variants in GATA1 or ALAS2 (Iolascon et al. 2020. PubMed ID: 32702750; Iolascon et al. 2013. PubMed ID: 23940284).

Patients with CDA can be both transfusion dependent or independent. Chronic hemolytic anemia can result in iron overload leading to liver damage, heart failure, diabetes, and hypergonadotropic hypogonadism. Genetics is helpful in differential diagnosis of CDA types from other forms of hemolytic anemia and from acquired versus inherited forms of dyserythropoiesis. Genetic diagnosis is achieved in ~80% of cases of CDA (Iolascon et al. 2020. PubMed ID: 32702750).

Majeed syndrome is a multisystemic inflammatory condition with patients also presenting with CDA (Ferguson and El-Shanti. 2021. PubMed ID: 33670882). Additional clinical information can be found on the LPIN2 test page. 

Genetics

CDA is inherited in an autosomal recessive manner through pathogenic variants in the CDAN1 (type I), CDIN1 (type I), and SEC23B (type II) genes. Missense pathogenic variants are predominant, and no patients homozygous for null pathogenic variants in either the CDAN1 or SEC23B genes have been documented. Consistent with this notion, Cdan1 knockout mice die in utero prior to erythropoiesis onset (Renella et al. 2011. PubMed ID: 21364188; Tao et al. 2012. PubMed ID: 22745161). Type III CDA is inherited in an autosomal dominant manner through pathogenic variation in the KIF23 gene with only one variant, c.2747C>G (p.Pro916Arg) being reported in a Swedish and an American family (Liljeholm et al. 2013. PubMed ID: 23570799). Type IV is due to KLF1 and GATA1 pathogenic variants associated with autosomal dominant and X-linked recessive forms of CDA type IV, respectively (Iolascon et al. 2020. PubMed ID: 32702750). Copy number variants are rare, with only one gross deletion being reported in the SEC23B and CDAN1 genes (Schwarz et al. 2009. PubMed ID: 19561605; Heimpel et al. 2006. PubMed ID: 16141353). De novo pathogenic variants are rarely reported in CDA cases (Iolascon et al. 2020. PubMed ID: 32702750). 

CDA has also been seen as a feature in some complex disorders including Majeed syndrome, developmental and epileptic encephalopathy, and macrocytic dyserythropoietic anemia. Majeed syndrome and developmental epileptic encephalopathy are inherited in an autosomal recessive manner due to pathogenic variants in the LPIN2 and CAD genes, respectively (Ferguson and El-Shanti. 2021. PubMed ID: 33670882; Russo et al. 2020. PubMed ID: 32720728). 

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

A genetic diagnosis is identified in ~80% of CDAs, with type II disease being most common. Pathogenic variants in SEC23B, CDAN1, CDIN1, GATA1, CAD and KLF1 account for 77.9%, 12.1%, 4%, 3.4%, 1.4%, and 1.4% of cases, respectively (Iolascon et al. 2020. PubMed ID: 32702750). Analytical sensitivity for the CDIN1, GATA1 and KLF1 genes should be high because all pathogenic variants reported to date are detectable by this method. 

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. 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

Testing for CDA is recommended for patients presenting with hemolytic anemia, reduced reticulocyte counts, and abnormal bone marrow examinations. In transfusion dependent cases, genetic testing is recommended to expedite diagnosis (Iolascon et al. 2020. PubMed ID: 32702750).

Genes

Official Gene Symbol OMIM ID
ALAS2 301300
CAD 114010
CDAN1 607465
CDIN1 615626
GATA1 305371
KIF23 605064
KLF1 600599
LPIN2 605519
SEC23B 610512
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
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Citations

  • Ferguson and El-Shanti. 2021. PubMed ID: 33670882
  • Heimpel et al. 2006. PubMed ID: 16141353
  • Iolascon et al. 2013. PubMed ID: 23940284
  • Iolascon et al. 2020. PubMed ID: 32702750
  • Liljeholm et al. 2013. PubMed ID: 23570799
  • Renella et al. 2011. PubMed ID: 21364188
  • Russo et al. 2020. PubMed ID: 32720728
  • Schwarz et al. 2009. PubMed ID: 19561605
  • Tao et al. 2012. 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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