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

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

Methods: 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.

Results: 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.

Conclusion: 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.
review, nhs, time, england, strategies, databases, diagnostic-tests, hfe gene, disorder, c282y, people, iron, outcome, h63d mutations, children, guidelines, family, london, publishing, population, dna, literature, validity, mutation, design, prevalence, disease, cost-effectiveness, outcomes, sensitivity and specificity, diagnosis, methods, systematic review
0022-2593
513-518
Bryant, J.
508f497c-8b5a-468f-a37d-be9c26e4e49d
Cooper, K.
ea064f58-d71d-404a-bcf3-49d243b8825b
Picot, J.
324d6f20-a105-49fd-9fb0-88791be84ada
Clegg, A.
838091f5-39df-4dbe-a369-675b26f2301b
Roderick, P.
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Rosenberg, W.
1a551f54-b4aa-42e0-a5e1-45c6a5232821
Patch, C.
1f70400a-854a-4c51-846d-47148fbb57e0
Bryant, J.
508f497c-8b5a-468f-a37d-be9c26e4e49d
Cooper, K.
ea064f58-d71d-404a-bcf3-49d243b8825b
Picot, J.
324d6f20-a105-49fd-9fb0-88791be84ada
Clegg, A.
838091f5-39df-4dbe-a369-675b26f2301b
Roderick, P.
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Rosenberg, W.
1a551f54-b4aa-42e0-a5e1-45c6a5232821
Patch, C.
1f70400a-854a-4c51-846d-47148fbb57e0

Bryant, J., Cooper, K., Picot, J., Clegg, A., Roderick, P., Rosenberg, W. and Patch, C. (2008) A systematic review of the clinical validity and clinical utility of DNA testing for hereditary haemochromatosis type 1 in at-risk populations. Journal of Medical Genetics, 45 (8), 513-518. (doi:10.1136/jmg.2007.055806). (PMID:18310265)

Record type: Article

Abstract

Objective: 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. Design: A systematic review.

Methods: 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.

Results: 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.

Conclusion: 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.

Full text not available from this repository.

More information

e-pub ahead of print date: 29 February 2008
Published date: August 2008
Keywords: review, nhs, time, england, strategies, databases, diagnostic-tests, hfe gene, disorder, c282y, people, iron, outcome, h63d mutations, children, guidelines, family, london, publishing, population, dna, literature, validity, mutation, design, prevalence, disease, cost-effectiveness, outcomes, sensitivity and specificity, diagnosis, methods, systematic review

Identifiers

Local EPrints ID: 69980
URI: https://eprints.soton.ac.uk/id/eprint/69980
ISSN: 0022-2593
PURE UUID: c1890877-f0f4-490c-8e6b-632e335942aa
ORCID for J. Picot: ORCID iD orcid.org/0000-0001-5987-996X
ORCID for P. Roderick: ORCID iD orcid.org/0000-0001-9475-6850

Catalogue record

Date deposited: 20 Jan 2010
Last modified: 20 Jul 2019 01:19

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