Juvenile Hereditary Hemochromatosis via the HFE2 (HJV) 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
7699 HJV 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7699HJV81479 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

Juvenile hereditary hemochromatosis (JHH) is a disorder characterized by excess iron overload with symptoms presenting within the first or second decade of life. Initial symptoms include lack of appetite, fatigue, amenorrhea, and arthralgia. Chronic iron deposition can lead to advanced disease including hypogonadotropic hypogonadism, hepatomegaly, cirrhosis, cardiomyopathy, arthropathy, and osteoporosis. In severe cases, JHH has led to lethal cardiac disease. Glucose intolerance has also been reported in about half of JHH cases. Early diagnosis of JHH is important as phlebotomy may be used to reduce iron levels and greatly reduces morbidity and mortality (Goldberg 2011; Lanzara et al. 2004; Santos et al. 2012).

Genetics

There are six types of hemochromatosis each due to a different genetic cause: type 1- HFE, type 2- HAMP or HFE2/HJV, type 3- TRF2, type 4- SLC40A1, type 5- FTH1, and type 6- FTL. Hemochromatosis is inherited in an autosomal recessive mode through pathogenic variants in the HFE, HAMP, HFE2/HJV, or TRF2 genes or an autosomal dominant pattern through pathogenic variants in the SLC40A1, FTH1, or FTL genes (Santos et al. 2012). Missense variants occurring in exons 3 and 4 of the HFE2/HJV gene are the most commonly reported pathogenic variants, with the c.959G>T (p.Gly320Val) variant being seen in greater than half of JHH cases. Small insertions and deletions have also been reported (Lanzara et al. 2004; Papanikolaou et al. 2003; Lee et al. 2004). No splice site alterations or gross deletions have been documented in the HFE2/HJV gene. Penetrance for JHH is greatly elevated compared to hereditary hemochromatosis via pathogenic variants in the HFE gene (Goldberg 2011). The HFE2/HJV gene encodes the protein hemojuvelin, which maintains iron hemostasis by inducing expression of the negative iron regulating protein, hepcidin (Lin et al. 2007).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a series of 34 patients with JHH, pathogenic variants in the HFE2/HJV were found in all cases (Lanzara et al. 2004). However, additional reports have suggest that pathogenic variants in the HAMP gene occur in >10% of JHH patients (Goldberg 2011). Analytical sensitivity should be high as all pathogenic variants in the HFE2/HJV gene reported to date are detectable by sequencing.

Testing Strategy

This test provides full coverage of all coding exons of the HFE2/HJV gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for testing include individuals with elevated serum ferritin concentration (1000 to 7000μg/L) and elevated transferrin-iron saturation. Individuals with JHH also may have MRI imaging indicating hepatic iron overload (Goldberg 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HJV.

Gene

Official Gene Symbol OMIM ID
HJV 608374
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hemochromatosis Type 2 AR 602390

Related Tests

Name
Hereditary Hemochromatosis Panel
Juvenile Hereditary Hemochromatosis via the HAMP Gene

Citations

  • 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
  • Lanzara C. et al. 2004. Blood. 103: 4317-21. PubMed ID: 14982873
  • Lee P.L. et al. 2004. Blood. 103: 4669-71. PubMed ID: 14982867
  • Lin L. et al. 2007. Blood. 110: 2182-9. PubMed ID: 17540841
  • Papanikolaou G. et al. 2004. Nature Genetics. 36: 77-82. PubMed ID: 14647275
  • Santos P.C. et al. 2012. International Journal of Molecular Sciences. 13: 1497-511. PubMed ID: 22408404

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

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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.
Total Price: $
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