Benchmarks for Cystic Fibrosis carrier screening: A European consensus document (original) (raw)

A 10-year large-scale cystic fibrosis carrier screening in the Italian population

Journal of Cystic Fibrosis, 2010

Background: Cystic Fibrosis (CF) is one of the most common autosomal recessive genetic disorders, with the majority of patients born to couples unaware of their carrier status. Carrier screenings might help reducing the incidence of CF. Methods: We used a semi-automated reverse-dot blot assay identifying the 47 most common CFTR gene mutations followed by DGGE/dHPLC analysis. Results: Results of a 10-year (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006) CF carrier screening on 57,999 individuals with no prior family history of CF are reported. Of these, 25,104 were couples and 7791 singles, with 77.9% from the Italian Veneto region. CFTR mutations were found in 1879 carriers (frequency 1/31), with ΔF508 being the most common (42.6%). Subjects undergoing medically assisted reproduction (MAR) had significantly (p b 0.0001) higher CF carrier frequency (1/22 vs 1/32) compared to non-MAR subjects. Conclusions: If coupled to counselling programmes, CF carrier screening tests might help reducing the CF incidence.

A survey of newborn screening for cystic fibrosis in Europe

Journal of Cystic Fibrosis, 2007

Background: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. Method: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. Results: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia™). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. Conclusions: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.

Health Technology Assessment Of The Genetic Tests For Cystic Fibrosis Carrier Screening in Italy

2018

Introduction: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CFTR gene. In Italy, the reported prevalence is approximately 0.70 per 10,000 inhabitants. Our aim was to summarize the available evidence, using the HTA approach, on the genetic tests for cystic fibrosis carrier screening. Methods: systematic literature search was used to find the best available international and national evidence on genetic tests for CF carrier screening. We addressed health problem of disease, description and technical characteristics of tests-its analytic and clinical validity, and clinical utility. Economic evaluation of different scenarios was synthesized from literature. Ethical, organizational, and social aspects of CF and genetic screening were also considered. Results: Several screening strategies have been evaluated in the literature and screening options can be characterized by different timing, model and place of screening. The reported cost of a screening test ranged from €25 to €212. Ethical analysis emphasized that the use of these tests is an advantage in terms of the acquisition of knowledge and of responsible management of choices, but at the same time raises many ethical questions. Social considerations reported an overall positive attitude among patients and their families towards CF carrier screening. Conclusions: Advances in the molecular genetics technology have made CF carrier testing reliable and affordable. The multidisciplinary approach of this HTA provided an evidence-based evaluation of the genetic tests and offers a firm scientific background for the decision-makers to consider the implementation of a screening for cystic fibrosis carriers into the Italian health care system.

Prenatal screening of Cystic Fibrosis: a single centre experience

Journal of prenatal medicine, 2008

The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and represent the most common autosomal recessive disease in the european population. We aimed to investigate the incidence of this condition during fetal life. In the past 10 years we examined in our centre 25393 fetuses of women underwent to amniocentesis. We carried out the examination of the most frequent mutations which enable, according to the literature data, the identification of almost 80% of the affected alleles. We identified 922 heterozygous and 9 homozygous for the mutation. The frequency of heterozygousin the examined sample was 1/27,5 while that of the affected was 1/2821. We encourage new thoughts regarding the diagnostic validity of the most frequent panel of mutations among the italian population in order to exclude never encountered mutations and the insertion of other more significant mutations.

The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2017

Newborn screening (NBS) for cystic fibrosis (CF) is a well-established public health strategy with international standards. The aim of this study was to provide an update on NBS for CF in Europe and assess performance against the standards. Questionnaires were sent to key workers in each European country. In 2016, there were 17 national programmes, 4 countries with regional programmes and 25 countries not screening in Europe. All national programmes employed different protocols, with IRT-DNA the most common strategy. Five countries were not using DNA analysis. In addition, the processing and structure of programmes varied considerably. Most programmes were achieving the ECFS standards with respect to timeliness, but were less successful with respect to sensitivity and specificity. There has been a steady increase in national CF NBS programmes across Europe with variable strategies and outcomes that reflect the different approaches.

Prenatal screening of Cystic Fibrosis: a single centre exeperience

2008

Objective: The gene responsible for the pathogenesis of cystic fibrosis has been known for over 15 years and represent the most common autosomal recessive disease in the european population. We aimed to investigate the incidence of this condition during fetal life. Methods: In the past 10 years we examined in our centre 25393 fetuses of women underwent to amniocentesis. We carried out the examination of the most frequent mutations which enable, according to the literature data, the identification of almost 80% of the affected alleles.

Cystic fibrosis screening: Lessons learned from the first 320,000 patients

Genetics in Medicine, 2004

Purpose: To examine the data from Ͼ 335,000 Cystic fibrosis (CF) tests to detect unsuspected findings and obtain clinical data when indicated to optimize genetic counseling. Methods: A proprietary database containing 335,204 consecutive CF DNA tests and 445 CF prenatal diagnostic tests was queried. Clinical information was obtained for prenatal and selected nonprenatal cases by telephone contact with physician offices. Results: The mutation 1078delT was found in much lower frequency than expected with rates of only 1:55,867 tests and 0.06% of CF mutations. This level is below the threshold set by the American College of Medical Genetics. Homozygosity was observed for 2789ϩ5GϾA in a 29-year-old women and compound heterozygosity with delta F408 in a 40-year-old woman with isolated chronic sinusitis. Many patients elected prenatal diagnosis when not at a 1:4 risk due to echogenic bowel or IVS-8 5T issues. Conclusions: With the exception of 1078delT, all CF mutations in the ACMG panel were detected with a frequency of Ͼ 0.1% of CF chromosomes. When ACMG guidelines are strictly adhered to, population-based CF carrier screening will accurately identify couples at risk for having children with CF. Genet Med 2004:6(3):136 -140.

Costs, effects, and savings of screening for cystic fibrosis gene carriers

Journal of Epidemiology & Community Health, 1998

Study objective-Evaluating the costs, eVects, and savings of several strategies for cystic fibrosis (CF) gene carrier screening. Design-A general model for evaluating prenatal, preconceptional, school, and neonatal carrier screening was constructed. For prenatal and preconceptional screening, two strategies were evaluated: single entry and double entry two step couple screening. Firstly, the Dutch situation was evaluated prospectively; subsequently the results were generalised to other carrier frequencies. Setting-Prospective simulation model. Main results-Of all screening strategies, neonatal carrier screening gives most carrier couples an informed choice concerning reproduction. If the parents of carrier newborns would not be tested however, prenatal screening detects most carrier couples. Prenatal and single entry preconceptional screening programmes have a favourable cost-savings balance in the Netherlands under a wide range of assumptions. For double entry preconceptional screening and neonatal screening, high enough values of uptake of screening, prenatal diagnosis, and induced abortion are necessary. School carrier screening does not have a favourable cost-savings balance. Conclusions-If a CF screening programme is judged to be useful on individual and social grounds, costs considerations are no obstacle for prenatal and single entry preconceptional screening.

Cystic fibrosis carrier screening effects on birth prevalence and newborn screening

Genetics in Medicine, 2015

We evaluated the effects of cystic fibrosis (CF) carrier screening on birth prevalence trends and newborn screening (NBS) efficiency by comparing two Italian regions; carrier screening was performed in one region (eastern region (ER)) and not in the other (western region (WR)). Methods: Annual births of infants with CF, NBS false-positive results, NBS uncertain diagnoses (borderline sweat chloride (BSC)), carrier tests performed, and carriers detected were monitored during the 1993-2013 period. Measurements and main results: A total of 259 newborns with CF were detected. In the ER, 150 carrier couples were found. Mean annual percentage of birth prevalence decrease was 9% per 10,000