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At least 19 recordsLinked to original sources

PubMed1997

Carrier screening for cystic fibrosis in primary care: evaluation of a project in South Wales. The South Wales Cystic Fibrosis Carrier Screening Research Team.

Population carrier screening for cystic fibrosis (CF) was offered to all patients aged 16-45 in one general practice in South Wales, excluding those in couples with a current pregnancy. Out of 1553 patients in this group, 481 subjects were tested, giving an overall uptake rate of more than 30%. The rate of uptake varied with the mode of invitation. Twenty-six carriers were identified, giving a prevalence of identified carriers of 5.4% (1 in 18.5) for those with no family history of CF. A further 18 carriers were identified by cascade testing of these 26. We describe the practical difficulties encountered in setting up this programme in primary care in South Wales. Questionnaires were administered or distributed to all subjects before and after testing. The response rate for the pre-test questionnaire was 95%, and 40-50% for the post-test questionnaires. These showed that, at 3 months post-test, 1 in 4 screen-negative subjects did not appreciate that they had a residual risk of being a carrier. At the same time, 15% of this group thought that there was a 1 in 4 chance of a child being affected if one parent was screen-positive (carried an identified mutation) and the other was screen-negative, and 40% thought there was no risk. Anxiety in relation to testing did not appear to be a major problem, although individual patterns of response to carrier status varied widely and more sensitive indicators of psychosocial impact of genetic tests are required. A pilot study of couple screening showed that this approach is unlikely to be useful in primary care, although we did not assess couple testing during pregnancy. For any programme of CF carrier screening to be established in primary care, it will be necessary to involve the primary care team from the earliest planning stage, so that the opportunity costs, training needs and other costs of the programme can be fully resourced.

Adolescent↗

PubMed2003

Update on population-based preconception and prenatal cystic fibrosis carrier screening.

Implementation of population-based cystic fibrosis (CF) carrier screening for all preconception and prenatal patients has encountered numerous challenges. Continuing education of the practitioner and patient is critical for ensuring the successful implementation of CF population-based carrier screening as well as other anticipated population-based molecular screening tests resulting from the completion of the Human Genome Project. To assist the practitioner, this article provides a brief review of cystic fibrosis genetics, the recommended screening guidelines and benefits of carrier screening, in addition to highlighting clinical dilemmas that have arisen since widespread CF carrier screening was initiated.

Cystic Fibrosis↗

PubMed1993

Antenatal cystic fibrosis carrier screening--whether, when and how?

Population screening for carriers of cystic fibrosis (CF) is now possible. Such screening may have both advantages and disadvantages and hence must be evaluated before it becomes routine practice. As the potential benefits of screening are wide and the drawbacks may include psychological effects, a combination of approaches is needed to assess screening thoroughly instead of only counting numbers of terminations or carrier tests. We describe the issues concerned and our methodology for a rigorous evaluation of population antenatal carrier screening for cystic fibrosis.

Anxiety↗

PubMedDate not supplied

CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations.

PURPOSE: We reviewed CFTR mutation distribution among Hispanic and African American individuals referred for CF carrier screening and compared mutation frequencies to those derived from CF patient samples. METHODS: Results from CFTR mutation analyses received from January 2001 through September 2003, were analyzed for four populations: Hispanic individuals with a CF diagnosis (n = 159) or carrier screening indication (n = 15,333) and African American individuals with a CF diagnosis (n = 108) or carrier screening indication (n = 8,973). All samples were tested for the same 87 mutation panel. RESULTS: In the Hispanic population, 42 mutations were identified: 30 in the patient population (77.5% detection rate) and 33 among carrier screening referrals. Five mutations not included in the ACMG/ACOG carrier screening panel (3876delA, W1089X, R1066C, S549N, 1949del84) accounted for 7.55% detection in patients and 5.58% among carriers. Among African American referrals, 33 different mutations were identified: 21 in the patient population (74.4% detection) and 23 in the carrier screening population. Together, A559T and 711+5G>A were observed at a detection rate of 3.71% in CF patients and 6.38% in carriers. The mutation distribution seen in both the carrier screening populations reflected an increased frequency of mutations with variable expression such as D1152H, R117H, and L206W. CONCLUSIONS: A detailed analysis of CFTR mutation distribution in the Hispanic and African American patient and carrier screening populations demonstrates that a diverse group of mutations is most appropriate for diagnostic and carrier screening in these populations. To best serve the increasingly diverse U.S. population, ethnic-specific mutations should be included in mutation panels.

Adolescent↗

PubMed1996

Lack of interest by nonpregnant couples in population-based cystic fibrosis carrier screening.

We used signs and letters to offer free cystic fibrosis (CF) carrier screening to nonpregnant adults in stable relationships who visited numerous clinical and nonclinical sites in Nashville. A total of 179 individuals (<<1% of those eligible) elected to be tested. To understand this observation, we used questionnaires to assess individuals' attitudes about genetic testing in general and about CF carrier screening in particular (n=873). Participants expressed conflicting views about carrier screening. More than 90% of people thought that genetic testing should at least be available. Most respondents said that the views of their partners and physicians were important in their decision making, and most believed that these others favored genetic testing. Yet, more than two-thirds indicated that such factors as insurability, being "at risk," what they would need to learn, abortion, and religious beliefs were important in their decision making, opinions that mitigated against genetic testing. In particular, one-third feared that carriers would lose their health insurance, one-quarter said that they would have been more interested had they been able to provide DNA by buccal swab rather than by finger stick, and less than one-sixth believed that genetic testing was meddling in God's plan. In the face of both the low level of use of free CF carrier screening by nonpregnant couples when it was not offered in person by health-care professionals and the wide variety of concerns demonstrated, we believe that clinicians should not routinely offer carrier screening to nonpregnant individuals who do not have a family history of CF.

Adult↗

PubMed1992

Principles and practicalities of carrier screening: attitudes of recent parents.

Population carrier screening for cystic fibrosis could soon be a reality, but we know very little about people's attitudes towards genetic disease in general or cystic fibrosis in particular. This paper reports a study which aimed to investigate some of these attitudes and also to explore feelings about CF carrier screening given its practical limitations. The results are discussed in the context of earlier studies which have not raised these practical issues.

Cystic Fibrosis↗

PubMed2000

Molecular diagnosis of and carrier screening for the neuronal ceroid lipofuscinoses.

The neuronal ceroid lipofuscinoses (NCLs) are a large group of autosomal recessive lysosomal storage disorders with both enzymatic deficiency and structural protein dysfunction. Three typical forms, the infantile (INCL), late-infantile (LINCL), and juvenile (JNCL), are among the most common childhood-onset neurodegenerative disorders. They result from mutations on genes CLN1, CLN2, and CLN3, respectively. We determined that the mutations 223A --> G and 451C --> T in CLN1, T523-1G --> C, and 636 C --> T in CLN2, and deletion of a 1.02-kb genomic fragment in CLN3 are the five common mutations for NCL. To offer clinical genetic testing for the NCLs, we have developed simple and quick PCR-based molecular tests for detecting INCL-, LINCL-, and JNCL-affected individuals from 180 NCL families (27 INCL, 76 LINCL, and 77 JNCL). The sensitivity of testing to detect NCL patients among clinically suspected individuals was determined to be 78% (21/27) for INCL, 66% (54/76) for LINCL, and 75% (58/77) for JNCL. When molecular screening for carriers was conducted among the normal siblings or parents of the probands, we identified two carriers out of three individuals tested for INCL, 20/56 (35.7%) carriers for LINCL, and 48/106 (45.3%) carriers for JNCL families. In addition, 5% (9/180) of NCL patients revealed genetic heterogeneity and were reclassified. Seven patients previously diagnosed as having JNCL were now found to carry mutations of CLN2 (5/7) or CLN1 (2/7) and 2 with late-infantile onsets were identified as carrying mutations of CLN1. Our data demonstrate the importance of DNA testing to detect accurately both affected individuals and carriers in NCL families.

Adolescent↗

PubMed1996

The views of general practitioners on community carrier screening for cystic fibrosis.

BACKGROUND: Recent developments in molecular genetics have made it possible to identify carriers of the cystic fibrosis (CF) mutation, regardless of family history, before they have an affected child. Using these techniques, population or 'community' carrier screening can offer informed reproductive choice to individuals and couples who would not otherwise know of their risk of having a CF child. AIM: This study set out to assess the views of general practitioners (GPs) on community carrier screening for CF and to consider the factors that influence their willingness to offer it themselves. METHOD: A self-administered questionnaires was sent to all 616 GPs in four areas of North Thames (West) Region. RESULTS: Two-thirds of respondents indicated that identifying carrier couples to offer genetic counselling before conception was a very important benefit of community carrier screening. Two-thirds felt that general practice was the most appropriate place in which to offer it, and similar proportions that the most appropriate times to do so were when a close relative was diagnosed and when seeking family planning. About half wanted to offer community carrier screening themselves; this was related to experience with CF patients and CF carrier testing, and estimates of the numbers of CF carriers in the practice. CONCLUSIONS: There is considerable support among GPs for community carrier screening for CF in general practice, particularly in the context of family planning services. Knowledge and experience of CF increase GPs' willingness to offer it themselves.

Attitude of Health Personnel↗

PubMed2006

A universal array-based multiplexed test for cystic fibrosis carrier screening.

Cystic fibrosis is a multisystem autosomal recessive disorder with high carrier frequencies in caucasians and significant, but lower, carrier frequencies in other ethnicities. Based on technology that allows high detection of mutations in caucasians and significant detection in other ethnic groups, the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG) have recommended pan-ethnic cystic fibrosis carrier screening for all reproductive couples. This paper discusses carrier screening using the Tag-It multiplex mutation platform and the Cystic Fibrosis Mutation Detection Kit. The Tag-It cystic fibrosis assay is a multiplexed genotyping assay that detects a panel of 40 cystic fibrosis transmembrane conductance regulator mutations including the 23 mutations recommended by the ACMG and ACOG for population screening. A total of 16 additional mutations detected by the Tag-It cystic fibrosis assay may also be common. The assay method is described in detail, and its performance in a genetics reference laboratory performing high-volume cystic fibrosis carrier screening is assessed.

Cell Membrane↗

PubMed1994

The cost-effectiveness of prenatal carrier screening for cystic fibrosis.

OBJECTIVE: To evaluate the economic consequences of routinely offering cystic fibrosis-carrier screening to pregnant white women under 35 years of age. METHODS: Decision analysis was used to evaluate the health outcomes and medical costs of a screening program from the health care payer's perspective. Probabilities were taken from the literature; cost data were based on consultations with laboratory and hospital administrators. Sensitivity analysis was performed for key assumptions. RESULTS: If the test acceptance rate were 78% and the screening test identified 85% of carriers, a prenatal cystic fibrosis-carrier screening program would identify slightly more than half of the high-risk pregnancies in the population. For a cohort of one million pregnant women, it would cost $83 million. If the proportion of couples choosing abortion were 30% and the lifetime cost of medical care for cystic fibrosis were $243,650, the program would save $12 million in averted costs of medical care for cystic fibrosis, for a net cost of $71 million. Even after accounting for the savings in averted medical care for cystic fibrosis, the cost per high-risk pregnancy identified would be $82,000; the cost per unwanted cystic fibrosis birth averted would be $1.4 million. Results were sensitive to the cost and sensitivity of the screening test, but relatively insensitive to the test acceptance rate and therapeutic abortion rates between 50-100% among pregnancies identified with cystic fibrosis. CONCLUSION: A prenatal cystic fibrosis-carrier screening program would not save the health care payer money under most assumptions, but may be justified if the benefit of the early information provided to expectant parents is judged worth the cost.

Abortion, Induced↗

PubMed1998

Tay-Sachs disease carrier screening: a model for prevention of genetic disease.

Tay-Sachs disease (TSD) is an autosomal-recessive, progressive, and ultimately fatal neurodegenerative disorder. Within the last 30 years, the discovery of the enzymatic basis of the disease, namely deficiency of the enzyme hexosaminidase A, made possible both enzymatic diagnosis of TSD and heterozygote identification. In the last decade, the cloning of the HEXA gene and the identification of more than 80 associated TSD-causing mutations has permitted molecular diagnosis in many instances. TSD was the first genetic condition for which community-based screening for carrier detection was implemented. As such, the TSD experience can be viewed as a prototypic effort for public education, carrier testing, and reproductive counseling for avoiding fatal childhood disease. More importantly, the outcome of TSD screening over the last 28 years offers convincing evidence that such an effort can dramatically reduce incidence of the disease.

Alleles↗

PubMed2025

A dataset of estimated heterozygous individual and carrier couple frequencies for pan-ancestry carrier screening.

The data described in this publication supported the development and evaluation of pan-ancestry reproductive carrier screening panels for autosomal recessive (AR) and X-linked (XL) conditions. Raw data included combined sets of DNA variants in 1,350 AR/XL genes obtained from the ClinVar and gnomAD databases. The dataset enabled calculations of positive yield for individuals and couples across both ancestry-specific and pan-ancestry, optimised "Goldilocks"-ranked gene panels, addressing population-specific variations in the frequencies of heterozygous individuals and carrier couples. The positive yield analysis offered a performance metric for carrier screening panels, facilitating the modeling of screening performance for panels of varying sizes and composition and providing resources for optimizing panel content to ensure equity across underrepresented genetic ancestries The dataset can support ongoing research into the equitable application of carrier screening and offers significant reuse potential for refining population genetic screening practices, validating computational models, and developing frameworks to update carrier screening panels in alignment with evolving genomic data, including in underrepresented and minority populations.

Carrier screening↗

PubMed2025

Optimizing gene panels for equitable reproductive carrier screening: The Goldilocks approach.

PURPOSE: Professional organizations recommend pan-ancestry carrier screening for autosomal recessive and X-linked conditions. Advances in DNA sequencing have allowed the analysis of hundreds of genes; however, the optimal number of genes for carrier screening remains unclear. The American College of Medical Genetics and Genomics (ACMG) has proposed a tiered approach recommending screening for 113 genes. METHODS: We analyzed ClinVar and gnomAD v4.1.0, for genes associated with serious autosomal recessive and X-linked conditions and modeled screening performance across panels of varying compositions and sizes in diverse genetic ancestries. We also reevaluated the ACMG gene list using the updated gnomAD data. RESULTS: We identified potential inconsistencies in the ACMG gene lists, particularly in the carrier test performance (defined as a positive yield) for underrepresented genetic ancestry groups. Modeling of the population data for 1310 genes revealed that the screening of 152, 248, 531, and 725 genes achieved 90%, 95%, 99%, and 99.7% positive yields, respectively, in couples. Real-world data from the screening of more than 60,000 couples were used to validate the model. CONCLUSION: Our methodology optimizes the gene content of carrier screening panels for diverse ancestry groups, provides a mechanism for continually updating guidelines, ensures consistency with genomic population data, and improves equity across populations.

Humans↗

PubMedDate not supplied

Cystic fibrosis carrier screening: knowledge and attitudes of prenatal care providers.

We are conducting a trial of population carrier screening for cystic fibrosis (CF), targeting pregnant and nonpregnant patients of prenatal care providers. We first enlisted providers by presenting a description of the trial to the obstetrical staffs of the five Rochester, New York, hospitals having delivery services. Of the 124 prenatal care providers (111 obstetricians and 13 family practitioners) with delivery privileges at the five hospitals, only 81 (65%) attended one of our presentations. Providers who attended lacked knowledge about CF screening and counseling and expressed divergent attitudes about prenatal diagnosis for carrier women having test-negative partners. Of the 79 providers completing an attitude questionnaire, 68 (86%) were willing to offer carrier screening to all their patients if educational materials, testing, and counseling were all provided without charge. After visiting participating physicians' offices to orient their staff, we reached two additional conclusions. First, in considering whether to offer CF carrier screening to their patients, prenatal care providers are less concerned about imperfect test sensitivity, false reassurance of those testing negative, or discrimination against those testing positive than about time required to answer patients' questions if they screen and about legal liability if they do not. Second, some providers are more resistant to offering screening to nonpregnant patients than to pregnant patients, not because they believe that the timing is less appropriate, but because nonpregnant patients do not routinely receive an advance mailing, have phlebotomy, or return for follow-up. Our experience raises concerns about the willingness and capability of prenatal care providers to translate advances in molecular medicine into prenatal screening services.

Attitude of Health Personnel↗

PubMedDate not supplied

Multimedia messages in genetics: design, development, and evaluation of a computer-based instructional resource for secondary school students in a Tay Sachs disease carrier screening program.

PURPOSE: Tay Sachs disease is a recessively inherited neurodegenerative disorder, for which carrier screening programs exist worldwide. Education for those offered a screening test is essential in facilitating informed decision-making. In Melbourne, Australia, we have designed, developed, and evaluated a computer-based instructional resource for use in the Tay Sachs disease carrier screening program for secondary school students attending Jewish schools. The resource entitled "Genetics in the Community: Tay Sachs disease" was designed on a platform of educational learning theory. METHODS: The development of the resource included formative evaluation using qualitative data analysis supported by descriptive quantitative data. The final resource was evaluated within the screening program and compared with the standard oral presentation using a questionnaire. Knowledge outcomes were measured both before and after either of the educational formats. RESULTS: Data from the formative evaluation were used to refine the content and functionality of the final resource. The questionnaire evaluation of 302 students over two years showed the multimedia resource to be equally effective as an oral educational presentation in facilitating participants' knowledge construction. CONCLUSION: The resource offers a large number of potential benefits, which are not limited to the Tay Sachs disease carrier screening program setting, such as delivery of a consistent educational message, short delivery time, and minimum financial and resource commitment. This article outlines the value of considering educational theory and describes the process of multimedia development providing a framework that may be of value when designing genetics multimedia resources in general.

Adolescent↗

PubMedDate not supplied

Preconception and prenatal cystic fibrosis carrier screening of African Americans reveals unanticipated frequencies for specific mutations.

PURPOSE: It is recommended that cystic fibrosis (CF) carrier screening be made available to African Americans who are either pregnant or planning a pregnancy. We analyzed the carrier and mutant allele frequencies for African Americans undergoing CF carrier screening in our laboratories. METHODS: Between December 2001 and September 2003, we performed carrier screening for 2189 African Americans, testing for at least the 25 recommended mutations. RESULTS: A total of 33 CF carriers were identified. The most common mutations detected were deltaF508, G622D, R117H/7T, and G551D. The G622D allele frequency among African Americans was 0.18%. We did not detect any 3120 + 1G --> A carriers, although 4 were expected (P < 0.05). CONCLUSIONS: When considering only the 25 recommended CF mutations, 1 in 75 African Americans screened in our laboratories were carriers (within the expected range, given a 69% mutation detection rate). The addition of 2 mutations, G622D and Q98R (incidentally identified while screening for ACOG/ACMG mutations), increased the observed carrier frequency to 1 in 66, which is not significantly different from the known African American carrier frequency of 1 in 65. The frequencies of several specific mutations detected were unanticipated, as was the absence of 3120 + 1G --> A carriers. Further studies on African American patients with classic CF are needed to examine the incidence of CF mutations that are not part of the current panel, such as G622D.

Black or African American↗

PubMed2005

Cost-effectiveness of a school-based Tay-Sachs and cystic fibrosis genetic carrier screening program.

PURPOSE: To explore the cost-effectiveness of school-based multi-disease genetic carrier screening. METHOD: Decision analysis of the cost-effectiveness of a school-based Tay-Sachs disease and cystic fibrosis genetic carrier screening program, relative to no screening. Data relating to ethnicity profile, test-accepting behavior, and screening program cost were sourced from an existing program in Sydney, Australia. RESULTS: Compared to no screening, the incremental cost-effectiveness of the screening program is A dollar 5,834 per additional carrier detected. This cost-effectiveness ratio is most sensitive to changes in genetic test accuracy, and the cost of laboratory assays. The results imply a cost per affected birth avoided of approximately A dollar 530,000 (approximately US dollar 371,000). CONCLUSIONS: This preconceptional genetic carrier screening program offers comparable cost-effectiveness to prenatal screening programs for cystic fibrosis.

Adolescent↗

PubMed2004

ACOG committee opinion. Number 298, August 2004. Prenatal and preconceptional carrier screening for genetic diseases in individuals of Eastern European Jewish descent.

Certain autosomal recessive disease conditions are more prevalent in individuals of Eastern European Jewish (Ashkenazi) descent. Previously, the American College of Obstetricians and Gynecologists recommended that individuals of Eastern European Jewish ancestry be offered carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis as part of routine obstetric care. Based on the criteria used to justify offering carrier screening for Tay-Sachs disease, Canavan disease, and cystic fibrosis, the American College of Obstetricians and Gynecologists' Committee on Genetics recommends that couples of Ashkenazi Jewish ancestry also should be offered carrier screening for familial dysautonomia. Individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders. Carrier screening is available for mucolipidosis IV Niemann-Pick disease type A, Fanconi anemia group C, Bloom syndrome, and Gaucher's disease.

Canavan Disease↗