A systematic review of the clinical validity and clinical utility of DNA testing for hereditary haemochromatosis type 1 in at-risk populations

Southampton Health Technology Assessments Centre, Mailpoint 728, Boldrewood, University of Southampton, Southampton SO167PX, UK.
Journal of Medical Genetics (Impact Factor: 5.64). 03/2008; 45(8):513-8. DOI: 10.1136/jmg.2007.055806
Source: PubMed

ABSTRACT To evaluate the clinical validity and clinical utility of DNA testing in people suspected of having hereditary haemochromatosis and in family members of those diagnosed with the disorder.
A systematic review.
15 electronic databases were searched up to April 2007. For assessment of the clinical validity of genotyping for the C282Y mutation in the diagnosis of hereditary haemochromatosis, studies were included if they reported the use of DNA tests in Caucasians of northern European origin with iron overload suggestive of haemochromatosis compared with a control population, and reported or allowed calculation of sensitivity and specificity. For clinical utility, studies were included if participants were Caucasians with iron overload suggestive of haemochromatosis or were relatives of suspected cases, if the study compared a diagnostic strategy incorporating DNA testing with one not incorporating DNA testing, and if the study reported patient-based outcomes or some measure of cost effectiveness.
11 studies that could be used to evaluate clinical validity of genotyping for the C282Y mutation in the diagnosis of hereditary haemochromatosis were identified. Clinical sensitivity of C282Y homozygosity for hereditary haemochromatosis ranged from 28.4% to 100%; when considering studies that used strict criteria to classify hereditary haemochromatosis clinical sensitivity ranged from 91.3% to 92.4%. No clinical effectiveness studies were found. Two cost effectiveness studies were identified, both of which suggested that gene testing may be cost effective.
DNA testing for hereditary haemochromatosis in at-risk populations has clinical validity and may have clinical utility. The review highlights the limitations of the literature and the methodological difficulties associated with evaluating this genetic test.

  • BMJ (online) 01/2011; 342:c7251. DOI:10.1136/bmj.c7251 · 16.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: The discovery of hemochromatosis genes and the availability of molecular-genetic tests considerably modified the knowledge of the disease relative to physiopathology, penetrance, and expression, and had major impact in the diagnostic settings. Areas covered: Hemochromatosis is a heterogenous disorder at both genetic and phenotypic level. The review discusses criteria to define patients' iron phenotype and to use molecular tests to diagnose HFE-related and non-HFE hemochromatosis. The material examined includes articles published in the journals covered by PubMed US National Library of Medicine. The author has been working in the field of iron overload diseases for several years and has contributed 18 of the papers cited in the references. Expert opinion: Hemochromatosis genotyping is inseparable from phenotype characterization. A full clinical assessment is needed and DNA test performed when data suggest a clear indication of suspicion of being at risk for HH. HFE testing for p.Cys282Tyr mutation and p.His63Asp variant is the first molecular diagnostic step. Genotyping for rare mutations can be offered to patients with negative first-level HFE testing who have iron overload with no other explanation and should be performed in referral centers for iron overload disorders that can provide genetic advice and in-house genotyping services.
    Expert Opinion on Medical Diagnostics 03/2013; 7(2):161-77. DOI:10.1517/17530059.2013.763794
  • Source
    British Journal of General Practice 06/2013; 63(611):331-2. DOI:10.3399/bjgp13X668410 · 2.36 Impact Factor