Eila K. Watson

Psychological and social consequences of community carrier screening programme for cystic fibrosis

We have assessed the effect of screening for cystic fibrosis (CF) carrier status on anxiety levels, attitudes, knowledge and actions of participants in a pilot programme conducted through primary health care services. Over 3000 individuals were screened and 100 carriers with no previous family history were identified. Varying degrees of anxiety were found to be associated initially with a positive result, but most of this was allayed by genetic counselling, and we find no adverse long-term psychological consequences in carriers. Most discussed carrier status with their partner (89%), parents, other relatives and also with friends; 87% of partners to whom testing was suggested have been screened. Those testing positive indicated that knowledge of carrier status would be considered in future reproductive decisions, and after 6 months carriers retained a reasonable level of knowledge about CF and its inheritance. Carriers and non-carriers uniformly approve of screening and are glad to have been tested. Knowledge of CF in the sample of non-carriers has also increased after testing, suggesting screening may improve understanding of CF among the entire target population. Fears of possible social costs of screening may be ill-founded.

FIRST-TRIMESTER PRENATAL DIAGNOSIS OF CYSTIC FIBROSIS WITH LINKED DNA PROBES

Linkage analysis with cloned gene probes has shown that the mutation causing cystic fibrosis is located in the middle of the long arm of chromosome 7. First-trimester diagnosis of cystic fibrosis is reported in four informative families and second-trimester diagnosis in one family with fetal DNA prepared from chorionic villi, hybridised with the tightly linked DNA probes, pJ3.11 and met. Risk calculations show that the expected false-negative and false-positive rates are approximately 2% and 6%, respectively, for typical nuclear families with one affected living child. Existing probes are sufficiently informative to allow full diagnosis in about two-thirds of couples presenting with at least one affected child. In half of the remainder, the inheritance of one parental mutant chromosome can be deduced.

Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless

An expressed gene sequence which was identified by the isolation of a methylation free CpG island from human chromosome 7 has been cloned from a human lung cDNA library. The deduced protein sequence contains 360 amino acids and has several features of a secreted protein; it is cysteine rich with a signal peptide sequence and two potential asn‐linked glycosylation sites. The protein sequence shows marked similarity with human and murine int‐1 and their Drosophila homolog wingless (Dint‐1). This human int‐1 related protein, int‐1 and Dint‐1 have diverse patterns of expression, but the inferred structural similarities suggest that some of the functional characteristics of these proteins may be shared.

A model system for the analysis of gene exclusion: cystic fibrosis and chromosome 19.

We have used multilocus analysis to exclude the cystic fibrosis locus from six polymorphic DNA markers covering most of chromosome 19. A substantial increase in the confidence for exclusion was obtained using the computer programme LINKAGE compared to analysis of pairwise lod scores. A structured approach to the analysis of linkage to autosomal recessive inherited diseases where the biochemical defect is not known is described.

A video to inform and reassure autonomous cystic fibrosis carriers identified by a community screening programme

Carrier screening programmes for cystic fibrosis have found that many of those identified as carriers are initially anxious about their result, although this generally declines after genetic counselling. This paper describes a project to try to reduce initial anxiety and the need for extensive post-test counselling through the production of a video to be sent in addition to the usual leaflet to individuals receiving a positive test result through the post. Fifty-five individuals were identified as cystic fibrosis carriers through a community screening programme and were sent the leaflet and video; 53 agreed to be interviewed and 52 also completed a follow-up questionnaire. The video was found to be an acceptable and effective way of providing information and support as part of an overall package including printed information and personal counselling.

The incidence of ΔF508 CF mutation, and associated haplotypes, in a sample of English CF families

SummaryData are presented for ΔF508 screening and KM19/XV2c haplotype analysis of 195 cystic fibrosis (CF) chromosomes from the British Caucasian population. We report the frequency of ΔF508 in this group to be 80% and find pronounced disequilibrium between the deletion and the KM 2, XV 1 haplotype. Haplotype analysis of 71 normal chromosomes is also presented. We report one individual who had meconium ileus and who does not have the ΔF508 mutation on either chromosome.

ΔF508 frequency and associated haplotypes near the cystic fibrosis locus in the Yugoslav population

SummaryChromosomes from 19 unrelated Southern Yugoslav families in which cystic fibrosis (CF) occurs were analysed for the presence of the ΔF508 mutation, using polymerase chain reaction amplification followed by dot blot and polyacrylamide gel analysis. Of the 38 CF chromosomes, 15 (39.5%) carry the ΔF508 deletion. Restriction fragment length polymorphism haplotypes for KM19/PstI, XV2c/TaqI and J3.11/PstI marker loci were determined and are compared for a total of 34 N and 37 CF chromosomes.