Performed

Monday - Friday

Methodology

Real-Time Polymerase Chain Reaction

Reported

Routine: 12 - 14 days

Synonyms

  • Hemochromatosis Gene
  • Hemochromatosis Mutation
  • HFE Gene
  • HFE Variant
  • HH
  • H63D
  • p.H63D
  • C282Y
  • p.C282Y
  • C845G>A
  • c.845G>A
  • c.187C>G
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

12 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     

Reference Interval

Not Detected: Negative for the HFE gene mutations tested, C282Y and H63D

Interpretive Data

HFE-associated hereditary hemochromatosis (HH) is an autosomal recessive disorder in which there is an inappropriately elevated absorption of iron via the gastrointestinal tract and progressive accumulation in various tissues. The disease is characterized by a broad phenotypic spectrum, from those with no clinical or biochemical evidence of iron overload to the most severely affected displaying end-organ damage due to iron deposition. Clinical manifestations of disease can include hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, arthropathy, and cardiomyopathy and/or arrhythmias.

Two common mutations found in the HFE gene include c.845G>A (p.C282Y) and c.187C>G (p.H63D). Clinical relevance is associated with homozygous (c.845G>A/c.845G>A; 60% to 90% of cases) and compound heterozygous (c.845G>A/c.187C>G; 3% to 8% of cases) genotypes. Homozygosity for c.187C>G (1% of cases) is not associated with the hemochromatosis phenotype in the absence of other modifying factors.

Incidence: The carrier frequency for a mutation in the HFE gene in individuals varies by ethnicity and is highest in individuals of European descent (6% for c.845G>A, 14% for c.187C>G).

Inheritance: Autosomal recessive with reduced penetrance (5% of c.845G>A homozygotes and <2% of c.845G>A/c.187C>G compound heterozygotes develop clinical disease).

Cause: The majority of HH patients have mutations in the HFE gene. The most common disease associated variant in the HFE gene is c.845G>A (p.C282Y). A second HFE variant, c.187C>G (p.H63D), has also been associated with HH.

Methodology: Polymerase chain reaction and fluorescence monitoring

Analytical Sensitivity and Specificity: 99%

Limitations: Variants other than HFE c.187C>G and c.845G>A will not be detected by this assay. Diagnostic error may occur with this test due to rare genetic variation at a primer binding site. A negative HFE test does not exclude a diagnosis of iron overload or hemochromatosis as clinically significant iron overload can occur in the absence of known HFE mutations. 

This test was developed and its performance characterictics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the US Food and Drug Administration. FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions.
Ordering

Performed

Monday - Friday

Methodology

Real-Time Polymerase Chain Reaction

Reported

Routine: 12 - 14 days

Synonyms

  • Hemochromatosis Gene
  • Hemochromatosis Mutation
  • HFE Gene
  • HFE Variant
  • HH
  • H63D
  • p.H63D
  • C282Y
  • p.C282Y
  • C845G>A
  • c.845G>A
  • c.187C>G
  • Clinical Genomics

Performing Lab

Clinical Genomics

Turnaround Time

12 days

Add-on Eligibility

Yes, within 7 days of collection
*If DNA has been extracted previously for other Clinical Genomics tests, this is stored for 6 weeks and may qualify for add-on
Collection

Specimen Type

Blood

Specimen Volume

5 mL (Minimum: 1 mL)

Collection Container

EDTA Whole Blood Tube (Lavender Top Vacutainer)

Unacceptable Conditions

  1. Severely clotted or grossly hemolyzed specimens
  2. Specimens that have been improperly collected, stored, or transported
  • Specimens collected in preservatives other than EDTA
    • ACD tubes are accepted, but EDTA is preferred
  • Serum or plasma
  • Specimens that have been frozen
  • Commingled specimens
  1. Specimens in tubes that have been damaged or broken during transport
  2. Specimens with insufficient volume for testing
  3. Unlabeled or mislabeled specimens

Storage/Transport Temperature

Transport Instructions      
Collection Location Transport Temperature Processing Required Timeframe
ED/Inpatient Room Temperature None Specimen must be received by the lab within 3 days of collection
Laboratory/Outpatient/Off-Site Room Temperature None Specimen must be received by the lab within 3 days of collection

Storage: Refrigerated

Stability (from collection to initiation)

Stability:
Prior to Extraction:
  • Room Temperature: 3 days
  • Refrigerated: 7 days
  • Frozen: Unacceptable
Extracted DNA:
  • Room Temperature: Unacceptable
  • Refrigerated: Unacceptable
  • Frozen: Indefinitely

Laboratory Storage: 
  • Original Specimen: Refrigerated
  • Extracted DNA: Frozen
Laboratory Retention: 
  • Original Specimen: 6 weeks
  • Extracted DNA: 6 weeks

Collection Instructions

Labeling Instructions:
When labeling blood tubes, leave a small window visible for the lab to assess the fill volume and sample integrity. Ensure that the barcode is in the correct orientation.


Collection Instructions:
Follow the correct order of draw when collecting with additional orders and tube types:
     
Result Interpretation

Reference Interval

Not Detected: Negative for the HFE gene mutations tested, C282Y and H63D

Interpretive Data

HFE-associated hereditary hemochromatosis (HH) is an autosomal recessive disorder in which there is an inappropriately elevated absorption of iron via the gastrointestinal tract and progressive accumulation in various tissues. The disease is characterized by a broad phenotypic spectrum, from those with no clinical or biochemical evidence of iron overload to the most severely affected displaying end-organ damage due to iron deposition. Clinical manifestations of disease can include hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, arthropathy, and cardiomyopathy and/or arrhythmias.

Two common mutations found in the HFE gene include c.845G>A (p.C282Y) and c.187C>G (p.H63D). Clinical relevance is associated with homozygous (c.845G>A/c.845G>A; 60% to 90% of cases) and compound heterozygous (c.845G>A/c.187C>G; 3% to 8% of cases) genotypes. Homozygosity for c.187C>G (1% of cases) is not associated with the hemochromatosis phenotype in the absence of other modifying factors.

Incidence: The carrier frequency for a mutation in the HFE gene in individuals varies by ethnicity and is highest in individuals of European descent (6% for c.845G>A, 14% for c.187C>G).

Inheritance: Autosomal recessive with reduced penetrance (5% of c.845G>A homozygotes and <2% of c.845G>A/c.187C>G compound heterozygotes develop clinical disease).

Cause: The majority of HH patients have mutations in the HFE gene. The most common disease associated variant in the HFE gene is c.845G>A (p.C282Y). A second HFE variant, c.187C>G (p.H63D), has also been associated with HH.

Methodology: Polymerase chain reaction and fluorescence monitoring

Analytical Sensitivity and Specificity: 99%

Limitations: Variants other than HFE c.187C>G and c.845G>A will not be detected by this assay. Diagnostic error may occur with this test due to rare genetic variation at a primer binding site. A negative HFE test does not exclude a diagnosis of iron overload or hemochromatosis as clinically significant iron overload can occur in the absence of known HFE mutations. 

This test was developed and its performance characterictics determined by the UC San Diego Health System Molecular Diagnostics Laboratory. It has not been cleared or approved by the US Food and Drug Administration. FDA clearance or approval is not required for clinical use. The result of this test should be interpreted using all relevant clinical data and should not be used alone for clinical diagnosis or patient management decisions.

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