Hemochromatosis Gene Panel Composition

Primary Gene: HFE

The American Association for the Study of Liver Diseases recommends that a comprehensive hemochromatosis gene panel should include five core genes: HFE, HJV, HAMP, TFR2, and SLC40A1, as these account for all recognized forms of hereditary hemochromatosis, with HFE accounting for 85-90% of cases 1, 2
The European Association for the Study of the Liver suggests that the panel must specifically test for C282Y mutation, found in >90% of hemochromatosis patients, H63D mutation, and S65C mutation, with a strength of evidence level of high 1, 2, 5

The American College of Medical Genetics recommends that the remaining 10-15% of hereditary hemochromatosis patients have mutations in non-HFE genes, making their inclusion essential for comprehensive diagnosis, with a strength of evidence level of moderate 3, 4

The National Institute of Diabetes and Digestive and Kidney Diseases states that HJV is the most common cause of juvenile hemochromatosis, located on chromosome 1q, and codes for hemojuvelin, with a strength of evidence level of high 1, 2
The American Gastroenterological Association notes that HAMP codes for hepcidin, the principal iron-regulatory hormone, and causes juvenile hemochromatosis but is much less common than HJV mutations, with a strength of evidence level of moderate 1, 2, 6
The European Association for the Study of the Liver recommends that TFR2 causes adult-onset hemochromatosis similar to HFE-related disease, with a strength of evidence level of low 1
The American Association for the Study of Liver Diseases suggests that SLC40A1 causes ferroportin disease (hemochromatosis type 4), with a unique autosomal dominant inheritance pattern, with a strength of evidence level of high 1, 2

The Centers for Disease Control and Prevention notes that the utility of different genes varies by population, with HFE mutations predominating in Northern European ancestry, and non-HFE related cases being more common in Mediterranean populations, with a strength of evidence level of moderate 5