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

ArticleinJournal of Medical Genetics 45(8):513-8 · March 2008with17 Reads
DOI: 10.1136/jmg.2007.055806 · Source: PubMed
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.
  • [Show abstract] [Hide abstract] ABSTRACT: To evaluate DNA testing for detecting hereditary haemochromatosis (HHC) in subgroups of patients suspected of having the disorder and in family members of those diagnosed with HHC. Major electronic databases, searched from inception to April 2007. A systematic review was undertaken using a priori methods and a de novo model developed to assess costs and consequences of DNA testing. Eleven studies were identified for estimating the clinical validity of genotyping for the C282Y mutation for the diagnosis of HHC. No clinical effectiveness studies meeting the inclusion criteria were identified. Two North American cost-effectiveness studies of reasonable quality were identified but their generalisability to the UK is not clear. Three cohort studies met the inclusion criteria for the review of psychosocial aspects. All had methodological limitations and their generalisability is difficult to determine. The clinical sensitivity of C282Y homozygosity for HHC ranged from 28.4% to 100%, or from 91.3% to 92.4% when considering only the most relevant studies. Clinical specificity ranged from 98.8% to 100%. One study found that gene testing was a cost-effective method of screening relatives of patients with haemochromatosis, whereas the other found that genotyping the spouse of a homozygote was the most cost-efficient strategy. Genetic testing for haemochromatosis appears to be well accepted, is accompanied by few negative psychosocial outcomes and may lead to reduced anxiety. The de novo economic model showed that, in people suspected of having haemochromatosis, the DNA strategy is cost saving compared with the baseline strategy using liver biopsy (cost saved per case detected 123 pounds), largely because of the reduction in liver biopsies. For family testing of siblings the DNA strategy is not cost saving because of the costs of the DNA test (additional cost per case detected 200 pounds). If the cost of the test were to reduce from 100 pounds to 60 pounds, the DNA strategy would be the cheaper one. For family testing of offspring the DNA test strategy is cheaper than the baseline biochemical testing strategy (cost saved per case detected 7982 pounds). Sensitivity analyses showed that the conclusions in each case are robust across all reasonable parameter values. The preferred strategy in practice is DNA testing in conjunction with testing iron parameters when there is clear clinical indication of risk for haemochromatosis because of biochemical criteria or when there is familial risk for HHC. Access to genetic testing and centralisation of test provision in expert laboratories would lower the cost of testing, improve the cost-effectiveness of the strategy and improve the quality of information provided to clinicians and patients.
    Full-text · Article · May 2009
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    Full-text · Article · Nov 2009
  • [Show abstract] [Hide abstract] ABSTRACT: • Some aspects of genetic health care (non-directive counselling, risk assessment and practical and emotional adjustment to the disorder) are unchanged by the explosion in genetic knowledge. • Three complex disorders: haemochromatosis, neural tube defects, schizophrenia, and their genetic counselling implications are discussed. • The role of genetic services in genetic susceptibility testing is less clear. • Accurate diagnosis, the ability to communicate the risk and precise risk estimation will remain important. KeywordsGenetic counselling-Susceptibility testing-Genetic tests
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