What is the role of genetic testing in diagnosis of haemochromatosis?

Worwood, Mark

doi:10.1258/0004563011900236

Cited by 12 publications

(7 citation statements)

References 77 publications

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“…These include: physician specialty and knowledge of rationale for HFE mutation testing; relationship of HFE genotype and initial diagnosis based on phenotyping; and perceived importance of HFE mutation testing in differential diagnosis. Previously reported indications for HFE mutation testing (Worwood, 2001) are consistent with outcomes of evaluation of liver abnormalities by gastroenterologists , and with outcomes of evaluation of abnormal serum iron measures at an iron disorders center as described herein.…”

Section: Hfe Mutations In Referred Specimens 301supporting

confidence: 74%

HFEGenotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

Acton

Barton²

2001

Genetic Testing

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We quantified HFE genotype frequencies in specimens submitted by physicians grouped by specialty and determined associations of genotypes with initial diagnosis based on phenotyping in patients evaluated at an iron disorders center. Of 526 specimens (519 from Alabama), these "typical" hemochromatosis-associated genotypes were detected: 85 C282Y/C282Y, 50 C282Y/H63D, and 27 H63D/H63D. Respective frequencies of C282Y/C282Y in specimens from an iron disorders center (n = 156), gastroenterologists (n = 147), hematologists/medical oncologists (n = 85), liver transplant surgeons (n = 11), endocrinologists and rheumatologists (n = 9), and "other sources" (n = 7) were greater (p < 0.05) than in population controls. In 44 patients from an iron disorders center initially diagnosed as "presumed hemochromatosis," 27 (61.4%) had C282Y/C282Y, 10 (22.7%) had C282Y/H63D, and 3 (6.8%) had H63D/H63D. C282Y/C282Y was not detected in 48 patients with "abnormality probably not an iron overload disorder." A total of 20.5% of 44 family members of patients had "typical" hemochromatosis-associated HFE genotypes (7.0% controls; p = 0.02). We conclude that most physicians who submitted specimens identify patients by phenotyping who have greater frequencies of "typical" hemochromatosis-associated HFE genotypes than controls, and that HFE mutation testing is useful in detecting hemochromatosis in family members of persons with hemochromatosis or iron overload.

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Section: Hfe Mutations In Referred Specimens 301supporting

confidence: 74%

HFEGenotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

Acton

Barton²

2001

Genetic Testing

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“…12 This test is straightforward because the 2 major HFE mutations alter restriction enzyme sites, allowing simple gene analysis by restriction enzyme digestion after polymerase chain reaction. 22 In centers that have conducted extensive pedigree studies, genetic testing for mutations of the HFE gene has found that more than 95% of typical patients with hemochromatosis are C282Y homozygotes. 19,20,23 This is a major advance over the diagnosis of HH based on degree of iron overload.…”

Section: Discussionmentioning

confidence: 99%

“…3 Genetic testing has the advantage of providing a definitive result regardless of the stage of iron overload and independent of dietary intake or tissue damage. 22 Genotyping provides greater than 99% sensitivity for a given mutation. 3 HH exhibits few specific signs or symptoms that alert the physician.…”

Section: Discussionmentioning

confidence: 99%

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Association of porphyria cutanea tarda with hereditary hemochromatosis

Mehrany¹,

Drage²,

Brandhagen³

et al. 2004

Journal of the American Academy of Dermatology

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“…If HH is diagnosed, periodic extractions of blood or therapeutic phlebotomy can prevent complications and provide normal life expectancy (Adams et al 1991;Niederau et al 1996). Therefore, successful diagnosis methods are vital to screen high-risk population groups for the disease (Njajou et al 2004;Worwood 2001).…”

Section: Introductionmentioning

confidence: 99%

On-chip HA/SSCP for the detection of hereditary haemochromatosis

Manage

Zheng

Somerville

et al. 2005

Microfluid Nanofluid

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Microfluidics provides a promising tool for meeting the growing demand for high-throughput and low-cost mutation detection technology. With conventional instrumentation, this need is often addressed by the combination of the single-strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) methods. This paper describes an effective microchipbased method to analyse the three most commonly tested gene mutations (C282Y, H63D, and S65C) associated with hereditary haemochromatosis by simultaneously performing microchip-based SSCP and HA, directly upon samples of polymerase chain reaction (PCR) product. We have increased the sensitivity of mutation detection considerably by adapting and combining SSCP with HA. We are able to perform the analysis within several minutes by avoiding off-chip sample preparation steps for SSCP and HA (apart from the PCR). The most important mutation in the screening of populations for this disease is the C282Y mutation and this mutation has not previously been detected with methods of HA/SSCP suitable for microchip implementation. This is, to the best of our knowledge, the first microchip-based test applying SSCP and HA for all three of the most common HFE mutations.

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What is the role of genetic testing in diagnosis of haemochromatosis?

Cited by 12 publications

References 77 publications

HFEGenotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

HFEGenotype Frequencies in Consecutive Reference Laboratory Specimens: Comparisons among Referral Sources and Association with Initial Diagnosis

Association of porphyria cutanea tarda with hereditary hemochromatosis

On-chip HA/SSCP for the detection of hereditary haemochromatosis

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