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Congenital Dyserythropoietic Anemia Type IV via the KLF1 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
11429 KLF1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11429KLF181479 81479,81479 $890 Order Options and Pricing

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

  • 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 pathogenic variants 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. Genetic testing 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. 2013; Tamary and Dgany 2009).

Type IV CDA is the third most common form with about 70 cases reported to date. The majority of these cases as part of a broader spectrum disorder such as Majeed syndrome, and mevalonate kinase deficiency. Type IV clinical presentation is heterogeneous and likely represents multiple unrelated disorders. However, due to relatively few patients, additional subclasses for type IV CDA have not been described (Iolascon et al. 2013).

Genetics

Type IV CDA is inherited in an autosomal dominant manner through pathogenic variants in the KLF1 gene. In 2010, the KLF1 gene was first documented to be involved in CDA. The c.937G>A (p.Glu325Lys) variant has been reported most frequently for type IV CDA. The KLF1 gene encodes an erythrocyte specific transcription factor, Krupple-like factor 1. The c.937G>A variant results in a dominant negative effect leading to impairment of KLF1 transcription activity and loss of Aquaporin 1 and CD44 expression (Araud et al. 2010). Severe transfusion dependent anemia has been reported in neonates with two pathogenic variants in the KLF1 gene (Viprakasit et al. 2014; Magor et al. 2015). Pathogenic variants in the KLF1 gene have also been associated with changes in hemoglobin levels, mainly increased expression of fetal hemoglobin (Gallienne et al. 2012).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity is unknown due to the small number of patients being reported to date. Analytical sensitivity for the KLF1 gene should be high because all pathogenic variants reported to date are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the KLF1 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. Electron microscopy indicating atypical cytoplasmic inclusions and enlarged nuclear pores is suggestive of type IV CDA. Patients with type IV CDA also presented with elevated fetal hemoglobin and nucleated erythrocytes with reduced CD44, BCAM, and ICAM4 surface expression (Arnaud et al. 2010; Viprakasit et al. 2014)

Gene

Official Gene Symbol OMIM ID
KLF1 600599
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Arnaud L. et al. 2010. American journal of human genetics. 87: 721-7. PubMed ID: 21055716
  • Gallienne AE. et al. 2012. Haematologica. 97: 340-3. PubMed ID: 22102705
  • Iolascon A. et al. 2013. Blood. 122: 2162-6. PubMed ID: 23940284 PubMed ID: 23940284
  • Magor GW. et al. 2015. Blood. 125: 2405-17. PubMed ID: 25724378
  • 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
  • Viprakasit V. et al. 2014. Blood. 123: 1586-95. PubMed ID: 24443441

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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