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Hereditary Spherocytosis Type 1 via the ANK1 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
11083 ANK1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11083ANK181479 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

Hereditary Spherocytosis (HS) is a condition where red blood cells lose their typical biconcave disc shape and appear spherical. It is characterized by anemia due to chronic extravascular hemolysis, jaundice, formation of bilirubin gallstones, reticulocytosis and splenomegaly (Aster et al. 2013). Disease symptoms can vary greatly with modest forms of the disease being most common (60-75% of cases). Mild forms of HS may be asymptomatic until adulthood, while more severe forms occur postnatally with life threatening anemia. There are five sub-types of HS with type I representing about half of HS cases defined by mutations in the ANK1 gene. Therapeutic intervention for severe cases includes partial splenectomy and/or regular transfusions to decrease hemolysis, increase hemoglobin levels, and limit development of bilirubin gallstones (Seims et al. 2013).

Genetics

Type 1 HS is inherited in an autosomal dominant and recessive manners due to mutations in the ANK1 gene. Disease severity ranges from mild to severe and is dependent on the extent of membrane defect. De novo mutations are found in approximately 30% of cases (Miraglia del Gudice et al. 2001). HS occurs in 1 in 2,000 individuals of Northern European ancestry and is less common in other ethnic backgrounds. Type I HS is solely defined by mutations throughout the ANK1 gene with the majority of mutations leading to premature termination (Gallagher and Forget 1998; Ozcan et al. 2003; Nakanishi et al. 2001). Substitution mutations at c. -153 and c.-108 within the upstream promoter region are also causative for disease (Gallagher et al. 2010). Mutations in SPTA1, SPTB, SLC4A1 and EPB42 also have been reported to cause HS and are responsible for ~40% of HS cases. The ANK1 gene encodes the protein ANKYRIN1 which tethers integral membrane proteins to the underlying spectrin-actin cytoskeleton allowing red blood cells to adopt a biconcave disc shape. The biconcave disc morphology is essential for providing flexibility to red blood cells enabling them to transverse narrow splenic capillaries.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing is capable of detecting >95% of mutations within the ANK1 gene. Mutations in the ANK1 gene are responsible for about half of HS cases (Aster et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the ANK1 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 for this test are patients showing features consistent with HR (spherocytes in peripheral blood smears, anemia and reticulocytosis) and a strong family history for the disorder. Other typical pathological features include increased mean corpuscular hemoglobin concentration, increased red cell distribution width, and heightened sensitivity in osmotic fragility test. HS may be differentiated from autoimmune and alloimmune hemolytic anemia via a negative Coombs test (Aster et al. 2013).

Gene

Official Gene Symbol OMIM ID
ANK1 612641
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hereditary Spherocytosis AD 182900

Citations

  • Aster, JC, Pozdnyakova, O, Kutok, JL. Hematopathology. Philadelphia: Elsevier Saunders, 2013.
  • Gallagher PG, Forget BG. 1998. Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis. Blood Cells Mol. Dis. 24: 539–543. PubMed ID: 9887280
  • Gallagher PG, Steiner LA, Liem RI, Owen AN, Cline AP, Seidel NE, Garrett LJ, Bodine DM. 2010. Mutation of a barrier insulator in the human ankyrin-1 gene is associated with hereditary spherocytosis. J. Clin. Invest. 120: 4453–4465. PubMed ID: 21099109
  • Miraglia del Giudice E, Nobili B, Francese M, D’Urso L, Iolascon A, Eber S, Perrotta S. 2001. Clinical and molecular evaluation of non-dominant hereditary spherocytosis. Br. J. Haematol. 112: 42–47. PubMed ID: 11167781
  • Nakanishi H, Kanzaki A, Yawata A, Yamada O, Yawata Y. 2001. Ankyrin gene mutations in japanese patients with hereditary spherocytosis. Int. J. Hematol. 73: 54–63. PubMed ID: 11372755
  • Ozcan R, Jarolim P, Lux SE, Ungewickell E, Eber SW. 2003. Simultaneous (AC)n microsatellite polymorphism analysis and single-stranded conformation polymorphism screening is an efficient strategy for detecting ankyrin-1 mutations in dominant hereditary spherocytosis. Br. J. Haematol. 122: 669–677. PubMed ID: 12899723
  • Seims AD, Breckler FD, Hardacker KD, Rescorla FJ. 2013. Partial versus total splenectomy in children with hereditary spherocytosis. Surgery 154: 849–855. PubMed ID: 24074424

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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