DNA icon

Hereditary Hemochromatosis via the HFE Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7697 HFE 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7697HFE81479 81479(x2) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

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 Hemochromatosis (HH) is an inherited iron overload disorder which, if untreated, may lead to progressive and potentially fatal organ dysfunction. Chronic iron deposition can result in advanced fibrotic liver disease, cirrhosis, hepatocellular carcinoma, atherosclerosis, arthritis, fatigue, diabetes, hypogonadism, cardiomyopathy, and diffuse skin pigmentation. Fatigue, impotence, and arthritis are the most commonly found symptoms (Vujic 2014; Leitman 2013). About 5 in every 1,000 western Caucasians have HH, although the majority are asymptomatic. Disease penetrance is variable with environmental factors such as nonalcoholic fatty liver disease, excessive alcohol consumption, and viral hepatitis hastening symptom onset. Symptom onset is typically after age 40 with men being more susceptible than women. There are six types of hemochromatosis each due to a different genetic cause: type 1- HFE, type 2- HAMP or HJV, type 3- TRF2, type 4- SLC40A1, type 5- FTH1, and type 6- FTL. Type 1 hemochromatosis is the most prevalent form of the disease and represents >90% of cases (Vujic 2014). Genetic testing can be helpful in differential diagnosis of HH from other liver function disorders and for determining the underlying cause of hemochromatosis (Zarrilli et al. 2013). Phlebotomy is standard treatment to reduce serum iron levels and prevent progressive liver damage.

Genetics

HH is inherited in an autosomal recessive manner through mutation in the HFE gene. Hemochromatosis may also been inherited in an autosomal recessive mode through mutations in the HAMP, HJV, or TRF2 genes or an autosomal dominant pattern through mutations in the SLC40A1, FTH1, or FTL genes. In patients identified with HH via transferrin saturation analysis, 60% of patients are homozygous for c.845G>A (p.Cys282Tyr), 8% homozygous for c.187C>G (p.His63Asp), and 7% are compound heterozygous for the two variants (de Villiers et al. 1999; Stuhrmann et al. 2010). The p.Cys282Tyr mutation disrupts an internal disulfide bond affecting the tertiary protein structure leading to intracellular degradation (Feder et al. 1996). The c.187C>G mutation (p.His63Asp) is a low penetrant mutation with homozygous individuals largely being asymptomatic (Sham et al. 2000). Other missense and nonsense mutations have been identified in the HFE gene in compound heterozygotes with the p.Cys282Tyr mutation (Piperno et al. 2000). Deletion of the entire HFE gene has been reported in two cases (Le Gac et al. 2008; Pelucchi et al. 2009). The HFE gene encodes the HFE protein which is sequestered by transferrin receptor 1 at the hepatocyte cell membrane to act as an iron sensing complex. In cases of iron overload, the HFE/transferrin complex will upregulate herpcidin expression which functions to regulate iron transport from the gut (Vujic 2014).

Clinical Sensitivity - Sequencing with CNV PG-Select

Variability in disease penetrance, criteria for diagnosis, and environmental factors contribute to difficulties in determining clinical sensitivity. In patients where HH is clearly defined and other causes of iron overload have been ruled out, clinical sensitivity is >90% in a study of Northern Europeans (Bryant et al. 2008). 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).

Testing Strategy

This test provides full coverage of all coding exons of the HFE gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with biochemical testing indicating transferrin saturation and elevated serum ferritin are candidates for testing (Qaseem et al. 2005; Sood et al. 2013). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HFE.

Gene

Official Gene Symbol OMIM ID
HFE 613609
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hemochromatosis Type 1 AR 235200

Related Tests

Name
Comprehensive Cardiology Panel
Hereditary Hemochromatosis Panel

Citations

  • 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
  • Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Ellis MC, Fullan A, Hinton LM, Jones NL, et al. 1996. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13: 399–408. PubMed ID: 8696333
  • Le Gac G. et al. 2008. Blood. 112: 5238-40. PubMed ID: 18809761
  • Leitman SF. 2013. Hemochromatosis: the new blood donor. ASH Education Program Book 2013: 645–650. PubMed ID: 24319245
  • Pelucchi S, Mariani R, Bertola F, Arosio C, Piperno A. 2009. Homozygous deletion of HFE: the Sardinian hemochromatosis? Blood 113: 3886–3886. PubMed ID: 19372266
  • Piperno A, Arosio C, Fossati L, Viganò M, Trombini P, Vergani A, Mancia G. 2000. Two novel nonsense mutations of HFE gene in five unrelated Italian patients with hemochromatosis. Gastroenterology 119: 441–445. PubMed ID: 10930379
  • Qaseem A, Aronson M, Fitterman N, Snow V, Weiss KB, Owens DK. 2005. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Annals of internal medicine 143: 517–521. PubMed ID: 16204164
  • Sham RL, Raubertas RF, Braggins C, Cappuccio J, Gallagher M, Phatak PD. 2000. Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles. Blood 96: 3707–3711. PubMed ID: 11090050
  • Sood R, Bakashi R, Hegade VS, Kelly SM. 2013. Diagnosis and management of hereditary haemochromatosis. British Journal of General Practice 63: 331–332. PubMed ID: 23735405
  • Stuhrmann M. et al. 2010. European Journal of Human Genetics : Ejhg. 18: N/A. PubMed ID: 20125190
  • Vujic M. 2014. Frontiers in Pharmacology. 5: 42. PubMed ID: 24653703
  • Zarrilli F. et al. 2013. Biomed Research International. 2013: 1-7. PubMed ID: 24222913

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

loading Loading... ×

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.
Total Price: $
×
Copy Text to Clipboard
×