Hereditary Hemochromatosis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10243 FTH1 81479,81479 Order Options
FTL 81479,81479
HAMP 81479,81479
HFE 81479,81479
HJV 81479,81479
SLC40A1 81479,81479
TFR2 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10243 Genes x (7) 81479 81479 $890 Order Options

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hereditary Hemochromatosis (HH) is a disorder characterized by excess iron overload, which, if untreated, can lead to progressive and potentially fatal organ dysfunction. Chronic iron deposition can result in liver cirrhosis, hepatocellular carcinoma, cardiomyopathy, diabetes, fatigue, and hypogonadism. There are six types of hemochromatosis, each due to a different genetic cause: type 1- HFE, type 2- HAMP or HFE2/HJV, type 3- TFR2, type 4- SLC40A1, type 5- FTH1, and type 6- FTL (Santos et al. 2012). Penetrance of type I HH is variable with many individuals remaining asymptomatic. Disease onset typically occurs after the fourth decade of life with penetrance for type I HH being influenced by other factors including alcohol consumption, fatty liver disease, and co-occurring pathogenic variants in other hemochromatosis related genes (Andersen et al. 2004). Type II HH, also referred to as juvenile HH, is a more severe form of disease with symptom onset occurring with the first or second decade of life. Phlebotomy is the standard treatment for HH and can minimize iron deposition leading to chronic disease. Genetic testing is helpful in the differential diagnosis of HH from other disorders presenting with iron overload including thalassemia, hemolytic anemia, chronic liver disease, and aceruloplasminemia (Bacon et al 2011).

Genetics

Hemochromatosis is inherited in an autosomal recessive manner through pathogenic variants in the HFE, HAMP, HFE2/HJV, or TFR2 genes or an autosomal dominant manner through pathogenic variants in the SLC40A1, FTH1, or FTL genes (Santos et al. 2012). Type I HH is the most common form. In patients identified with type I HH via transferring saturation analysis, 60% of patients are homozygous for c.845G>A (p.Cys282Tyr), 8% homozygous for c.187C>G (p.His63Asp), and 7% compound heterozygous for these two variants in the HFE gene (de Villiers et al. 1999; Stuhrmann et al. 2010). Co-occurring pathogenic variants in the HAMP and HFE2/HJV genes have been reported in individuals with more severe forms of type I HH (Jacolot et al. 2004; Le Gac et al. 2004). Other forms of HH exhibit higher but variable penetrance for disease compared to type I HH. See individual test descriptions for additional information on the molecular biology of each gene.

Testing Strategy

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.

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

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity for detection of causative variants in the HFE gene is >95% as gross gene deletions have been reported in very few cases (Le Gac et al. 2008). HJV, HAMP, SLC40A1, TFR2, FTH1, and FTL analytical sensitivity is >99%. In patients where type I HH is clearly defined and other causes of iron overload have been ruled out, clinical sensitivity is >90% in Northern Europeans (Bryant et al. 2008). In a series of 34 patients with juvenile HH, pathogenic variants in HFE2/HJV were found in all cases (Lanzara et al. 2004). However, additional reports suggest that pathogenic variants in the HAMP gene occur in >10% of juvenile HH patients (Goldberg 2011). Clinical sensitivity for the TFR2, FTH1, and FTL genes is currently unknown due to the small number of patients reported to date.

Indications for Test

The American Association for the Study of Liver Diseases recommends genetic testing of individuals with transferrin saturation levels greater than 45% and with serum ferritin levels greater than 200 ng/ml in males and 150 ng/ml in females (Bacon et al. 2011). Individuals with MRI imaging indicating hepatic iron overload are also candidates for testing (Goldberg 1993).

Genes

Official Gene Symbol OMIM ID
FTH1 134770
FTL 134790
HAMP 606464
HFE 613609
HJV 608374
SLC40A1 604653
TFR2 604720
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Andersen R.V. et al. 2004. Blood. 103: 2914-9. PubMed ID: 15070663
  • Bacon B.R. et al. 2011. Hepatology (baltimore, Md.). 54: 328-43. PubMed ID: 21452290
  • Bryant J. et al. 2008. Journal of Medical Genetics. 45: 513-8. PubMed ID: 18310265
  • de Villiers J.N. et al. 1999. Human Molecular Genetics. 8: 1517-22. PubMed ID: 10401000
  • Goldberg Y.P. 2011. Juvenile Hereditary Hemochromatosis. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301349
  • Jacolot S. et al. 2004. Blood. 103: 2835-40. PubMed ID: 14670915
  • Lanzara C. et al. 2004. Blood. 103: 4317-21. PubMed ID: 14982873
  • Le Gac G. et al. 2004. Human Molecular Genetics. 13: 1913-8. PubMed ID: 15254010
  • Le Gac G. et al. 2008. Blood. 112: 5238-40. PubMed ID: 18809761
  • Santos P.C. et al. 2012. International Journal of Molecular Sciences. 13: 1497-511. PubMed ID: 22408404
  • Stuhrmann M. et al. 2010. European Journal of Human Genetics : Ejhg. 18: N/A. PubMed ID: 20125190

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

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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