Hereditary Xerocytosis via the PIEZO1 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
11583 PIEZO1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11583PIEZO181479 81479(x2) $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.

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 Xerocytosis (HX), also called dehydrated hereditary stomatocytosis, is a mild to moderate form of hemolytic anemia characterized by dehydrated red blood cells. The dehydrated red blood cell phenotype is due to defects in cation permeability rendering cells susceptible to lysis via shear stress (Platt et al. 1981). HX primarily presents in adults with mild anemia and symptoms including fatigue, macrocytosis, reticulocytosis, splenomegaly, jaundice, and cholelithiasis (Albuisson et al. 2013). Genetic testing is helpful in the differential diagnosis of HX from other forms of hemolytic anemia including hereditary spherocytosis, hemoglobinopathies, and enzyme deficiency anemias including pyruvate kinase deficiency. Early diagnosis is often helpful in monitoring of cholelithiasis and prevention of iron overload through regular monitoring of serum ferritinemia (An and Mohandas 2008).

In autosomal recessive forms of the disease, severe lymphatic dysplasia with non-immune hydrops fetalis has been reported in perinatal patients with widespread lymphedema, pleural effusions, chylothoraces, and/or pericardial effusions. This form of the disease is phenotypically similar to other generalized lymphatic dysplasia disorders including Hennekam Lymphagiectasia-Lymphedema syndrome (Fotiou et al. 2015). Pseudohyperkalemia has also been reported in patients with HX. Due to the defect in cation permeability, blood samples stored at room temperature result in hyperkalemia lab results (Iolascon et al. 1999; Grootenboer et al. 1998).

Genetics

HX is inherited in an autosomal dominant manner through pathogenic variants in the PIEZO1 and KCNN4 genes. PIEZO is a mechanically activated cation channel that facilitates potassium and sodium transport. Gain of function missense variants in the PIEZO1 gene lead to increased permeability of cations resulting in HX (Albuisson et al. 2013; Andolfo et al. 2013). Missense variants are primarily located between exons 16-24 and 42-51. An in-frame deletion has also been reported in PIEZO1 gene for HX patients (Andolfo et al. 2013). In patients with HX, decreased osmotic fragility is present in individuals with pathogenic variants, however, clinical presentation is variable (Andolfo et al. 2013; Albuisson et al. 2013). Lymphatic dysplasia with non-immune hydrops fetalis via the PIEZO1 gene is inherited in an autosomal recessive manner. Missense, nonsense, and splice site alterations resulting in loss of PIEZO function have been reported (Lukacs et al. 2015; Fotiou et al 2015). Similar hematologic phenotypes are seen in morpholino knockdown of piezo1 in zebrafish (Faucherre et al. 2014).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity for the PIEZO1 gene is currently unknown due to the limited number of cases reported to date. In HX kindreds with pathogenic variants in the PIEZO1 gene, individuals with the familial variant presented with decreased osmotic fragility indicative of disease (Albuisson et al. 2013). Analytical sensitivity for the PIEZO1 gene should be high as all pathogenic variants to date are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the PIEZO1 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

HX candidates for testing present with an increase in mean corpuscular hemoglobin concentration decreased osmotic resistance, normal hemoglobin level, decreased haptoglobin and normal mean cell volume. Peripheral blood smears show hyperchromatic red blood cells and some presence (<10%) of stomatocytes (Albuisson et al. 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PIEZO1.

Gene

Official Gene Symbol OMIM ID
PIEZO1 611184
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Lymphedema, Hereditary, III AR 616843
Xerocytosis, Hereditary AD 194380

Citations

  • Albuisson J. et al. 2013. Nature Communications. 4: 1884. PubMed ID: 23695678
  • An X., Mohandas N. 2008. British Journal of Haematology. 141: 367–375. PubMed ID: 18341630
  • Andolfo I. et al. 2013. Blood. 121: 3925-35, S1-12. PubMed ID: 23479567
  • Faucherre A. et al. 2014. Haematologica. 99: 70-5. PubMed ID: 23872304
  • Fotiou E. et al. 2015. Nature Communications. 6: 8085. PubMed ID: 26333996
  • Grootenboer S. et al. 1998. British Journal of Haematology. 103: 383-6. PubMed ID: 9827909
  • Iolascon A. et al. 1999. Blood. 93: 3120-3. PubMed ID: 10216110
  • Lukacs V. et al. 2015. Nature Communications. 6: 8329. PubMed ID: 26387913
  • Platt O.S. et al. 1981. The Journal of Clinical Investigation. 68: 631-8. PubMed ID: 7276163

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.
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