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Hereditary Spherocytosis/Elliptocytosis via the SPTB 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
11713 SPTB 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11713SPTB81479 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

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Hereditary Spherocytosis (HS), also known as Minkowski-Chauffard disease, affects one in 2,000 individuals. HS is a condition where red blood cells lose their typical biconcave disc shape and appear spherical. The spherical appearance impairs membrane flexibility making it hard for red blood cells to transverse narrow capillaries, especially in the spleen. This impairment causes anemia due to chronic extravascular hemolysis, jaundice, formation of bilirubin gallstones, reticulocytosis and splenomegaly characteristic of HS disease (Aster et al. 2013; An and Mohandas 2008). Disease severity can range with 20-30% having mild form, 60-70% having moderate form, and 10-20% having severe form of HS. People with mild forms may be asymptomatic whereas severe forms of the disease present in newborns with life threatening anemia and require blood transfusions. There are five types of HS defined by the gene mutation causative for disease: Type I-ANK1, type 2-SPTB, type 3-SPTA1, type 4-SLC4A1, and type 5-EPB42 (Bolton-Maggs et al. 2004; Delaunay 2007). Patients with mutations in the SPTB gene tend to have mild to moderately severe HS (An and Mohandas 2008).

Hereditary Elliptocytosis (HE) is a milder red blood cell membrane disorder affecting one in 5,000 individuals. Red blood cells in these patients are elongated into cigar or oval shape with flexibility being impaired less than individuals with HS. The majority of patients are asymptomatic with ~10% having moderate to severe anemia and intermittent episodes of hemolysis, jaundice, and splenomegaly. Symptoms may present at 4-6 months in severe cases but usually resolve by 6-12 months. Severe HE may present with hereditary pyropoikilocytosis with newborns presenting with hemolytic anemia and requiring frequent blood transfusions. Elliptocytosis may be prominent in other disorders including iron deficiency, leukemia, megaloblastic anemia, myelofibrosis, sickle cell disease, thalassemia, and polycythemia. Therefore, genetic testing is helpful in differential diagnosis of these diseases (Gallagher 2004).


HS in inherited in an autosomal dominant manner in 75% of cases through mutations in the ANK1, SPTB, and SLC4A1 genes. Autosomal recessive forms are inherited through mutations in the ANK1, SPTA1, and EPB42 genes (Bolton-Maggs et al. 2004). Most mutations reported to date are private with de novo dominant mutations being six times more common than recessive mutations (Miraglia del Giudice et al. 2001). Mutations in the ANK1, SPTB, SLC4A1, SPTA1, and EPB42 genes account for 60%, 10%, 15%, 10%, and 5% cases of HS respectively (An and Mohandas 2008).

HE is inherited in an autosomal dominant manner through mutation in the SPTA1 (65% of cases), SPTB (30% of cases), or EPB41 (5% of cases) genes. HE with hereditary pyropoikilocytosis is caused by homozygous recessive or compound heterozygous mutations in SPTA1, SPTB, and EPB41 genes. De novo mutations are rarely reported (Gallagher 2004).

HS type 2 and HE is inherited in an autosomal dominant manner through mutations in the SPTB gene. Together the SPTA1 and SPTB genes encode alpha and beta spectrin proteins. These proteins form head to tail helical dimers and link red blood cell membrane proteins to actin to maintain membrane elasticity (Gimm et al 2002). Missense, nonsense, and splice site mutations are most commonly found within the SPTB gene for both HS and HE. Generally, missense mutations residing within the N-terminus of the α-spectrin protein are associated with HS whereas C-terminus mutations are associated with HE (Tse and Lux 1999). Missense N-terminal mutations often result in unstable transcripts and disrupt interactions with vertical protein 4.1 (Becker et al. 1993) whereas C-terminal mutations affecting protein function less.

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the SPTB gene are causative for 10% of HS and 30% of HE cases (An and Mohandas 2008; Gallagher 2004). NextGen sequencing analytical sensitivity is >95% for detection of causative mutations. Gross deletions and complex rearrangements have been reported, but are involved in <5% of HS cases.

Testing Strategy

This test provides full coverage of all coding exons of the SPTB 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 MCHC, increased RDW, and heightened sensitivity via osmotic fragility test. HS may be differentiated between autoimmune and alloimmune hemolytic anemia via a negative Coombs test (Aster et al. 2013).


Official Gene Symbol OMIM ID
SPTB 182870
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Elliptocytosis 3 182870
Spherocytosis, type 2 AD 616649


  • An X, Mohandas N. 2008. Disorders of red cell membrane. Br. J. Haematol. 141: 367–375. PubMed ID: 18341630
  • Aster, JC, Pozdnyakova, O, Kutok, JL. Hematopathology. Philadelphia: Elsevier Saunders, 2013.
  • Becker PS, Tse WT, Lux SE, Forget BG. 1993. Beta spectrin kissimmee: a spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1. J. Clin. Invest. 92: 612–616. PubMed ID: 8102379
  • Bolton-Maggs PHB, Langer JC, Iolascon A, Tittensor P, King M-J, General Haematology Task Force of the British Committee for Standards in Haematology. 2012. Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update. Br. J. Haematol. 156: 37–49. PubMed ID: 22055020
  • Delaunay J. 2007. The molecular basis of hereditary red cell membrane disorders. Blood Rev. 21: 1–20. PubMed ID: 16730867
  • Gallagher PG. 2004. Hereditary elliptocytosis: spectrin and protein 4.1R. Semin. Hematol. 41: 142–164. PubMed ID: 15071791
  • Gimm JA, An X, Nunomura W, Mohandas N. 2002. Functional characterization of spectrin-actin-binding domains in 4.1 family of proteins. Biochemistry 41: 7275–7282. PubMed ID: 12044158
  • 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
  • Tse WT, Lux SE. 1999. Red blood cell membrane disorders. Br. J. Haematol. 104: 2–13. PubMed ID: 10027705


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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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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