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Hereditary Spherocytosis/Elliptocytosis via the SPTA1 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
SPTA1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11711SPTA181479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

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 SPTA1 gene tend to have severe HS (Wichterle et al 1996).

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 3 is inherited in an autosomal recessive manner and HE in an autosomal dominant manner through mutations in the SPTA1 gene. Together the SPTA1 and SPTB genes encode alpha and beta spectrin proteins, respectively. 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 mutations at the N-terminus of α-spectrin are most common for both HS and HE and disrupt interactions with β-spectrin (Gaetani et al. 2008). Splicing mutations, most notably the c.4339-99C>T known as α-spectrin LEPRA, are the second most common group of causative mutations and result in premature protein termination (Wichterle et al. 1998). Nonsense mutations and large deletions have each only been reported in one case (Iolascon et al. 2011; Tolpinrud et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in the SPTA1 gene are causative for ~5% of HS and 65% of HE cases (Ah and Mohandas 2008; Gallagher 2004). NextGen sequencing analytical sensitivity is >95% for detection of causative mutations. Gross deletions have been reported in only a single case (Iolascon et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the SPTA1 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).

Testing includes detection of the c.4339-99C>T, α-spectrin LEPRA variant.

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 HS (Spherocytes in peripheral blood smears, anemia and reticulocytosis) and a 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). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SPTA1.


Official Gene Symbol OMIM ID
SPTA1 182860
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Elliptocytosis 2 AD 130600
Spherocytosis, Type 3 AR 270970


  • 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.
  • 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
  • Gaetani M, Mootien S, Harper S, Gallagher PG, Speicher DW. 2008. Structural and functional effects of hereditary hemolytic anemia-associated point mutations in the alpha spectrin tetramer site. Blood 111: 5712–5720. PubMed ID: 18218854
  • 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
  • Iolascon A, King M-J, Robertson S, Avvisati RA, Vitiello F, Asci R, Scoppettuolo MN, Delaunay J. 2011. A genomic deletion causes truncation of ?-spectrin and ellipto-poikilocytosis. Blood Cells Mol. Dis. 46: 195–200. PubMed ID: 21212007
  • 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
  • Tolpinrud W, Maksimova YD, Forget BG, Gallagher PG. 2008. Nonsense mutations of the alpha-spectrin gene in hereditary pyropoikilocytosis. Haematologica 93: 1752–1754. PubMed ID: 18815189
  • Wichterle H, Hanspal M, Palek J, Jarolim P. 1996. Combination of two mutant alpha spectrin alleles underlies a severe spherocytic hemolytic anemia. J. Clin. Invest. 98: 2300–2307. PubMed ID: 8941647


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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