Objective
The original objectives of the Concerted Action were as follows:
1. Distribution of large numbers of standardised primers, ASOs and control DNA to member labs and a set of references for these
2. Distribution of knowledge through workshops and newsletters
3. Development of database
4. Development of a quality control programme
5. Staff exchange programme to allow travel between member labs.
Within each European Community (EC) country a single major advisory lab has been designated as a reference centre within the country with the aim of providing a long term knowledge base within each European country. A regular newsletter was produced to provide information on methods of mutation detection, mutation analysis data, population screening studies, quality control and mutation frequency reports. Reagents have been distributed to member laboratories enable them to screen for a large range of mutations.
Information has been collated on mutation incidence by laboratory and by population allowing manipulation of data to provide recent usable data on mutations that laboratories may find in their populations, and indication of which primers should be provided. A second database for assessment of needs of each laboratory, includes information on population, techniques and equipment used in each laboratories, particular projects being undertaken (ie population screening) and allows for easy collection, integration and distribution of information on each laboratory. A third database records information on family histories, mutation analysis, unidentified mutations and turn around times within laboratories.
A quality control programme was established allowing member laboratories to participate in an external process to check their procedures and techniques using reagents of known quality. Links with industry have been established and, as a result, each of the reference laboratories has been given several hundred standard cystic fibrois test kits and on site training by one company (ICI).
Cystic Fibrosis is the most common of the severe inherited diseases of children in most European countries. It also occurs at slightly lower levels among these from the Middle East and the Indian sub-continent, but is almost unknown in Africa, Japan and China. In Europe itself, the incidence varies from approximately 1 in 1000 in Brittany to 1 in 4000 in Denmark; in general the incidence is of the order of 1 in 2500 across Europe. There are approximately 10 million carriers in Europe and 25000 affected young people, many of whom are seriously ill. Pulmonary obstruction and infection are the most life threatening clinical manifestations for those affected by the disease. Most patients have exocrine pancreatic dysfunction, and neonatal meconium ileus occurs in 5-10% of cases. Other manifestations include cirrhosis of the liver, infertility (especially in males), and abnormally high levels of sweat chloride and sodium.
The mutation causing CF was localised to chromosome 7 by scientific groups at St Mary's London, Toronto and Salt Lake City in 1985 and the gene, known as CFTR (cystic fibrosis transmembrane conductance regulator) and the most common mutation (a three base pair deletion DF508 in one of the regulatory protein sequences of CFTR) were reported by the Toronto group in 1989. This mutation accounts for 70-90% of the CF mutations in most Northern European countries, but only about 30-60% of the mutations in Italy, Spain and Portugal. Although over 150 different mutations causing cystic fibrosis have now been found, only a few are common, and over 85% of CF carriers can be identified in most European countries, with the exception of Southern European countries, where about 70% of carriers can be identified by testing for four or five gene mutations.
Fields of science
Topic(s)
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CON - Coordination of research actionsCoordinator
W2 1PG London
United Kingdom