Analytic validity of cystic fibrosis testing: A preliminary estimate

Palomaki, Glenn E.; Bradley, Linda; Richards, C. Sue; Haddow, James E.

doi:10.1097/00125817-200301000-00003

Cited by 25 publications

(29 citation statements)

References 7 publications

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“…An estimate of the analytical sensitivities and specificities for CFTR mutation analysis from the same PT program for the years 1996 through 2001 was 97.9 and 98.4%, respectively. 7 This is considerably lower than the measured sensitivity and specificity of 98.8 and 99.6%, respectively, from the more current data from 2003 through 2013 summarized in this report. Possible explanations for the observed improvement in analytic performance include ongoing participation in an external PT program, improvement in testing technologies, and/or the standardization of mutations tested.…”

Section: Discussionmentioning

confidence: 55%

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys

Lyon

Schrijver

Weck

et al. 2015

Genetics in Medicine

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Section: Discussionmentioning

confidence: 55%

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys

Lyon

Schrijver

Weck

et al. 2015

Genetics in Medicine

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“…Overall, however, the error rate has been low. 12 The one laboratory using DNA sequencing methodology was able to analyze the entire CFTR gene in our product, and even detected an unexpected (although common) M470V polymorphism in all of the samplesapparently carried by whatever person had donated DNA for construction of these BACs in the early years of the Human Genome Project.…”

Section: Discussionmentioning

confidence: 92%

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

Jarvis

Iyer

Williams

et al. 2005

The Journal of Molecular Diagnostics

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The lack of readily available, patient-derived materials for molecular genetic testing of many heterozygous or rare disorders creates a major impediment for laboratory proficiency and quality control procedures. The paucity of clinically derived mutation-positive samples could be surmounted if it were possible to construct artificial samples containing mutations of interest that would sufficiently resemble natural human samples. Such samples could then function as acceptable and realistic performance evaluation challenges and quality control reagents for recipient laboratories. Using the cystic fibrosis gene (CFTR) as a prototype, we have devised and executed experiments designed to generate unique DNA samples that could be used for these purposes. We used site-directed mutagenesis to generate mutations of interest in plasmid DNA derived from common bacterial artificial chromosome sources containing the cystic fibrosis transmembrane conductance receptor gene. CFTR mutations G85E and 1078delT were chosen to represent mutations in the original American College of Medical Genetics-recommended populationscreening panel of 25 mutations. DNA samples containing predetermined concentrations and ratios of wild-type and mutated plasmids, bacterial artificial chromosomes of interest, and nonhuman genomic carrier DNA were characterized and tested in-house and in a group of nine pilot testing laboratories using a variety of technical platforms. The results indicate that these constructs, containing CFTR mutations in heterozygous and homozygous states, can serve as valid and accessible materials for quality assurance, including performance evaluation, proficiency test-

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“…5 The strengths and weakness of using this data source versus other data sources have been previously described. 6 The ACMG/CAP survey includes nearly all clinical laboratories in the U.S. that utilize a wide range of HFE testing methodologies. The survey samples have confirmed genotypes and are tested blindly.…”

Section: Methodsmentioning

confidence: 99%

“…The analytic validity of CFTR testing in the setting of prenatal screening for cystic fibrosis has been published. 6 For example, consider the identification of non-Hispanic Caucasians carriers of a cystic fibrosis mutation. Even though the analytic sensitivity and specificity for CFTR testing are slightly lower than for HFE testing reported in the present study, the high carrier rate for cystic fibrosis (1 in 25) results in a similar analytic positive predictive power (75%) to that found for C282Y homozygosity (66%).…”

Section: Analytic Validity Of Hfe Testing For Homozygositymentioning

confidence: 99%

Estimated analytic validity of HFE C282Y mutation testing in population screening: The potential value of confirmatory testing

Palomaki

Haddow

Bradley

et al. 2003

Genetics in Medicine

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Purpose: The purpose of this study was to estimate analytic sensitivity and specificity of HFE testing for C282Y homozygosity in the hypothetical setting of population screening for hemochromatosis. Analytic sensitivity for C282Y homozygosity is 98.4% (95% CI 95.9%-99.5%). The analytic specificity is 99.8% (99.4%-99.9%). At a frequency of 40 per 10,000 for the homozygous genotype, the analytic positive predictive value is 66%. Conclusion: HFE testing for C282Y homozygosity is highly reliable. Homozygosity is uncommon in population screening, however, and confirmatory testing should be considered. Genet Med 2003:5(6):440 -443.

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Analytic validity of cystic fibrosis testing: A preliminary estimate

Cited by 25 publications

References 7 publications

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys

Molecular genetic testing for cystic fibrosis: laboratory performance on the College of American Pathologists external proficiency surveys

A Novel Method for Creating Artificial Mutant Samples for Performance Evaluation and Quality Control in Clinical Molecular Genetics

Estimated analytic validity of HFE C282Y mutation testing in population screening: The potential value of confirmatory testing

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