Medical genetic testing in the United States.
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Genetic Testing↗
Biomedical subjects
Linda A Bradley
Publications and source records attributed to Linda A Bradley.
Genetic testing for susceptibility to breast and ovarian cancer: evaluating the impact of a direct-to-consumer marketing campaign on physicians' knowledge and practices.
PURPOSE: To assess the impact of direct-to-consumer marketing of genetic testing for risk of breast and ovarian cancer by a biotechnology company on: 1) physicians' knowledge; 2) reasons given when asking questions about the test; and 3) physicians' practice patterns in two pilot cities where the campaign took place and two control cities. METHODS: Survey of randomly selected family physicians, internists, obstetrician-gynecologists, and oncologists from May 1-May 21, 2003. RESULTS: Physicians' knowledge did not differ between pilot and control cities. Significant differences (pilot versus control cities) were seen in the reasons patients gave for asking questions about testing. More physicians in pilot cities (14%) than control cities (7%) reported an increase in the number of times they ordered genetic testing for breast and ovarian cancer risk in the previous 6 months (adjusted odds ratio 1.9, 95% confidence interval, 1.2-3.1). Awareness of professional guidelines and being in a practice with a policy on genetic testing for risk of breast and ovarian cancer were associated with physicians' behaviors and interest among patients in testing. CONCLUSIONS: Given the complexity and limitations of genetic testing for risk of breast and ovarian cancer, the development and broad dissemination of clinical guidelines and education of physicians are needed.
Breast Neoplasms↗
From genetics to genomics: using gene-based medicine to prevent disease and promote health in children.
The remarkable achievements of the Human Genome Project promise great opportunities for disease prediction, treatment, and prevention. In this paper, we discuss the continuum of genetic variation as medical practice begins to shift focus from the study of single genes (genetics) to the study of the entire genome (genomics). Pediatricians should anticipate an influx of genetic information and will need to become as facile in interpreting this type of predictive information as they are with other types of medical data, while recognizing the unique ethical, legal, and social implications of genetic testing in children. We discuss an approach to assist pediatricians in decision-making that emphasizes the need for knowledge about the analytic performance of genetic tests, their validity in predicting health outcomes, and the utility of the genetic information in improving health and preventing disease.
Adolescent↗
Updated assessment of cystic fibrosis mutation frequencies in non-Hispanic Caucasians.
PURPOSE: To update estimates of individual and cumulative cystic fibrosis (CF) mutation frequencies in non-Hispanic Caucasians for the prenatal screening panel recommended by American College of Medical Genetics and to determine the impact on screening performance. METHODS: Two data sources were used. In the first (CF Genetic Analysis Consortium), our re-analysis was restricted to North American studies. In the second (CF Foundation National Patient Registry), we performed a new analysis restricted to individuals tested at eight Therapeutic Development Network sites. RESULTS: The updated average cumulative proportion of mutations identified is 88.34% (higher than previously reported), indicating that 78% of high-risk couples (and affected fetuses) can potentially be identified. CONCLUSION: Prenatal CF screening in U.S. non-Hispanic Caucasians is more effective than previously thought.
Cystic Fibrosis↗
Standards and guidelines for CFTR mutation testing.
One mission of the ACMG Laboratory Quality Assurance (QA) Committee is to develop standards and guidelines for clinical genetics laboratories, including cytogenetics, biochemical, and molecular genetics specialties. This document was developed under the auspices of the Molecular Subcommittee of the Laboratory QA Committee by the Cystic Fibrosis (CF) Working Group. It was placed on the "fast track" to address the preanalytical, analytical, and postanalytical quality assurance practices of laboratories currently providing testing for CF. Due to the anticipated impact of the ACMG recommendation statement endorsing carrier testing of reproductive couples, it was viewed that CF testing would increase in volume and that the number of laboratories offering CF testing would also likely increase. Therefore, this document was drafted with the premise of providing useful information gained by experienced laboratory directors who have provided such testing for many years. In many instances, "tips" are given. However, these guidelines are not to be interpreted as restrictive or the only approach but to provide a helpful guide. Certainly, appropriately trained and credentialed laboratory directors have flexibility to utilize various testing platforms and design testing strategies with considerable latitude. We felt that it was essential to include technique-specific guidelines of several current technologies commonly used in laboratories providing CF testing, since three of the four technologies discussed are available commercially and are widely utilized. We take the view that these technologies will change, and thus this document will change with future review.
Cystic Fibrosis↗
Hereditary hemochromatosis: perspectives of public health, medical genetics, and primary care.
Hereditary hemochromatosis (HHC) is a condition characterized by excess iron in body tissues, resulting in complications such as cirrhosis, cardiomyopathy, diabetes, and arthritis. These complications usually manifest during adulthood. Two methods of screening for the detection of early stage of HHC are available: serum iron measures and molecular testing to detect mutations in the gene. These phenotypic and genotypic screening tests are of particular interest because a simple treatment-periodic phlebotomy-can be used to prevent iron accumulation and clinical complications. HHC might represent the first adult-onset genetic disorder for which universal population-based screening would be appropriate. Therefore, HHC has been proposed as a paradigm for the introduction of adult genetic diseases into clinical and public health practice. However, universal screening for HHC has not been recommended because of the uncertainty about the natural history of the iron overload or HHC and, in particular, uncertainty about the prevalence of asymptomatic iron overload and the likelihood that it will progress to clinical complications. If universal screening is not appropriate based on current data, what other measures might reduce the disease burden of iron overload? New studies provide more systematic information about the penetrance of the C282Y mutation and shed further light on the natural history of the disorder. The authors review these data and consider their implications for public health, medical genetics, and primary care.
Genetic Testing↗
Analytic validity of cystic fibrosis testing: a preliminary estimate.
PURPOSE: Derive estimates of analytic sensitivity and specificity of DNA testing for cystic fibrosis in the United States. METHODS: Analyze published results of the American College of Medical Genetics (ACMG)/College of American Pathologists (CAP) Molecular Genetics Survey between 1996 and 2001, taking into account difficult, simulated clinical samples included for educational purposes. RESULTS: Analytic sensitivity is 97.9% [95% confidence interval (CI) 96.8-98.7%], and analytic specificity is 99.4% (95% CI 98.7-99.9%) after removing challenges involving delI507 and performing other adjustments. Analytic sensitivity is consistent over the 6 years. Specificity was lower in 1997. CONCLUSION: These preliminary estimates indicate that analytic validity of cystic fibrosis testing is very good and can likely be improved. To date, fewer than half of the mutations in the panel recommended for preconceptional or prenatal screening have been challenged. The present study highlights the value of performing confirmatory testing when a mutation is identified to reduce false-positive results.
Alleles↗
Technical standards and guidelines: prenatal screening for open neural tube defects.
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Amniotic Fluid↗
Estimated analytic validity of HFE C282Y mutation testing in population screening: the potential value of confirmatory testing.
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. METHODS: We analyzed published results of the Molecular Genetics Survey performed by the American College of Medical Genetics/College of American Pathologists between 1998 and 2002, taking into account its educational nature. RESULTS: 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.
Genetic Testing↗
Technical standards and guidelines: prenatal screening for Down syndrome.
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Biomarkers↗
Technical standards and guidelines: venous thromboembolism (Factor V Leiden and prothrombin 20210G >A testing): a disease-specific supplement to the standards and guidelines for clinical genetics laboratories.
These standards and guidelines are designed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to this statement does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical molecular geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the laboratory record the rationale for any significant deviation from these standards and guidelines.
Factor V↗