Spherocytosis/Elliptocytosis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10233 ANK1 81479,81479 Order Options and Pricing
EPB41 81479,81479
EPB42 81479,81479
SLC4A1 81479,81479
SPTA1 81479,81479
SPTB 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10233Genes x (6)81479 81479 $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 PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Hereditary Spherocytosis (HS), also known as Minkowski-Chauffard disease, is the most common form of hemolytic anemia due to red blood cell membrane defects. HS is a condition where red blood cells lose their hallmark biconcave disc shape leading to formation of spherocytes. Spherocytes have impaired flexibility making it difficult for red blood cells to transverse narrow capillaries, especially in the spleen. This impairment causes anemia due to chronic extravascular hemolysis resulting in jaundice, hyperbilirubinemia, gallstones, reticulocytosis and splenomegaly (Aster et al. 2013; An et al. 2008. PubMed ID: 18341630). Disease severity ranges with 20-30% of HS patients having mild, 60-70% having moderate, and 10-20% having severe forms of HS. Autosomal dominant HS typically result in mild to moderate HS compared to recessive HS primarily being moderate to severe. People with mild forms may be asymptomatic whereas severe forms of the disease present in newborns with severe anemia requiring blood transfusions. There are five types of HS defined by the causative gene for disease: Type I-ANK1, type 2-SPTB, type 3-SPTA1, type 4-SLC4A1, and type 5-EPB42 (Bolton-Maggs et al. 2012. PubMed ID: 22055020; Delaunay. 2007. PubMed ID: 16730867). HS affects one per 2,000 individuals.

Hereditary Elliptocytosis (HE) is a milder red blood cell membrane disorder affecting one in 5,000 individuals and is most commonly found in individuals of African, Mediterranean or Southeast Asian descent (Nagel and Roth. 1989. PubMed ID: 2669996). Red blood cells in these patients are elongated into an oval shape with flexibility being impaired less than individuals with HS. Subtypes of HE include hereditary pyropoikilocytosis (HPP) and Southeast Asian ovalocytosis (SAO). The majority of patients are asymptomatic with a few 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. Newborns with HPP often present with hemolytic anemia and require frequent blood transfusions. Individuals with SAO present with a stomatocytic elliptocytosis red blood cell morphology and may exhibit mild anemia. About half of SAO neonates present with hyperbilirubinemia which resolves in early childhood (Laosombat et al. 2010. PubMed ID: 20421175).

Elliptocytosis and spherocytes have been reported in other disorders including iron deficiency, leukemia, megaloblastic anemia, myelofibrosis, sickle cell disease, thalassemia, and polycythemia therefore genetic testing is helpful in differential diagnosis (Gallagher. 2004. PubMed ID: 15071791).

Genetics

HS in inherited in an autosomal dominant manner in 75% of cases through pathogenic variants in the ANK1, SPTB, and SLC4A1 genes. Autosomal recessive forms are primarily inherited through pathogenic variants in the SPTA1 gene (Bolton-Maggs et al. 2012. PubMed ID: 22055020). A founder variant in Eastern Europeans, designated c.4339-99C>T or Lepra, is the most commonly found pathogenic variant in the SPTA1 gene. In general, truncating variants in the SPTB gene are associated with autosomal dominant forms of HS, whereas missense variants are more commonly found in autosomal recessive forms. Most pathogenic variants reported to date in HS related genes are private truncating variants (Park. 2016. PubMed ID: 26830532; Wang. 2018. PubMed ID: 29572776). Pathogenic variants in the ANK1, SPTB, SLC4A1, SPTA1, and EPB42 genes account for 60%, 10%, 15%, 10%, and 5% cases of HS respectively (An et al. 2008. PubMed ID: 18341630). About 30% of HS cases are sporadic with no family history.

HE is inherited in an autosomal dominant manner via the SPTA1 (65% of cases), SPTB (30% of cases), or EPB41 (5% of cases) genes. HPP is caused by homozygous recessive or compound heterozygous variants in the SPTA1 gene (Gallagher. 2004. PubMed ID: 15071791). A 27bp deletion in the SLC4A1 gene, denoted c.1199_1225del (p.Ala400_Ala408del), is a founder variant frequently found in patients with SAO (Laosombat et al. 2010. PubMed ID: 20421175). Autosomal recessive HS is also inherited via the SPTB, EPB41, and EPB42 genes.

The ANK1, SPTB, SLC4A1, SPTA1, EPB42 and EPB41 genes encode proteins that help to maintain the biconcave disc morphology in red blood cells through connections between the spectrin cytoskeleton and membrane proteins (Bolton-Maggs et al. 2012. PubMed ID: 22055020).

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

Clinical Sensitivity - Sequencing with CNV PGxome

In a study of HS patients of Korean descent, pathogenic variants in the ANK1 or SPTB genes were identified in 21 of 25 patients with over half of the cases being de novo (Park et al. 2016. PubMed ID: 26830532). A separate study identified causative pathogenic variants in 50 of 59 HS patients using an NGS panel approach (Choi et al. 2019. PubMed ID: 31122244). Analytical sensitivity is >95%.

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.

Sequencing will also cover 500 bp upstream of the ANK1 start codon and the SPTA1 Lepra/Prague region, c.4339-99C>T (Miraglia del Giudice et al. 2001. PubMed ID: 11167781).

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for testing include individuals with Coombs-negative hemolytic anemia, presence of spherocytes on blood smears, a positive osmotic fragility test, and increased MCHC. A positive family history is present in about ~75% cases of HS. Red blood cell indices vary depending on the severity of HS (Aster et al. 2013).

Genes

Official Gene Symbol OMIM ID
ANK1 612641
EPB41 130500
EPB42 177070
SLC4A1 109270
SPTA1 182860
SPTB 182870
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • An et al. 2008. PubMed ID: 18341630
  • Aster et al. 2013. Hematopathology. Philadelphia: Elsevier Saunders.
  • Bolton-Maggs et al. 2012. PubMed ID: 22055020
  • Choi et al. 2019. PubMed ID: 31122244
  • Delaunay. 2007. PubMed ID: 16730867
  • Gallagher. 2004. PubMed ID: 15071791
  • Laosombat et al. 2010. PubMed ID: 20421175
  • Miraglia del Giudice et al. 2001. PubMed ID: 11167781
  • Nagel and Roth. 1989. PubMed ID: 2669996
  • Park. 2016. PubMed ID: 26830532
  • Wang. 2018. PubMed ID: 29572776

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.

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

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ORDER OPTIONS

View Ordering Instructions

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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.

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