Layla N. Al-Jader

Survey of attitudes of pregnant women towards Down syndrome screening.

This study aimed to examine whether pregnant women made informed decisions based on an accurate understanding of the antenatal screening process and to explore their attitude to screening and termination of a Down syndrome fetus. Womens aspirations were the keystone that informed the development of the first strategy for antenatal screening for congenital anomalies. Semi‐structured interviews were carried out with a sample of pregnant women in South Wales in 1995. A total of 34 women aged less than 35 years, who were 20 weeks pregnant, were interviewed. These women were selected because the screening policy differed between hospitals for this age group. The majority of women were not aware that screening tests were voluntary: tests were presented as routine. About half of the sample were not well informed to make decisions. Only five out of a sampling frame of 101 women refused screening; they tended to be better educated and of higher social class. All women wanted to be given the choice whether to be screened. Seven out of 34 would not terminate an affected fetus. Staff communication skills, especially in delivering risk estimate, were criticized. The survey findings supported the view that women required an information package tailored to their individual needs. Copyright

Severity of chest disease in cystic fibrosis patients in relation to their genotypes.

A detailed comparison of the severity of chest disease with mutational status was carried out by cross sectional study of 127 cystic fibrosis patients, aged 1 to 31 years, living in Wales. Lung disease was classified according to severity, depending on pulmonary function tests (carried out on 76 patients) and chest radiograph status; information was obtained also on age at diagnosis in relation to severity of chest disease and colonisation with Pseudomonas species. Genotypes were determined by analysis for the mutations delta F508, delta I507, G551D, R553X, G542X, R117H, R560T, 1717--IG > A, and 621 + 1G > T. CF patients homozygous positive and heterozygous for the delta F508 deletion showed a significant decline of lung function with age. Unlike other studies, we did not find patients homozygous positive for the delta F508 deletion to have poorer lung function compared with heterozygous patients. Patients with the genotype 621 + IG > T/delta F508 tended to have more severe chest disease than the delta F508 homozygous patients in the same age group. There was some evidence that four patients heterozygous for R117H have mild chest disease.

The Frequency of Inherited Disorders Database: Prevalence of Huntington Disease

A database of the frequency of human inherited disorders is being established for use in a clinical context, in medical research, for epidemiological studies, and in the planning of genetic services. Each entry includes the disease name categorized by organ system, an Online Mendelian Inheritance in Man (OMIM) number, the mode of inheritance, the population origin, a prevalence and/or incidence rate and a literature reference. The Frequency of Inherited Disorders Database (FIDD) currently contains 1,580 entries relating to 280 different Mendelian disorders. FIDD will be prospectively maintained and can be accessed at http://www.uwcm.ac.uk/uwcm/mg/fidd/. A more refined and systematic literature search that will serve to expand the size, scope and scale of the database is currently in progress. The coverage of neurological and neuromuscular disorders is however considered to be nearly complete. In this first description of FIDD, Huntington disease was used to illustrate the structure and scope of the database as well as its potential scientific utility. A total of 100 published articles on the prevalence of Huntington disease were appraised. Prevalence and incidence rates varied between different ethnic groups and between different countries. Possible reasons for this variation are discussed.

Mutation analysis of 184 cystic fibrosis families in Wales.

We describe a molecular analysis of 184 cystic fibrosis (CF) families in Wales. To determine accurate frequency data for the CF mutations in the Welsh population, families with at least three Welsh grandparents were strictly regarded as Welsh. Of these 74 families, we have identified approximately 90% of mutations causing CF, with delta F508 accounting for 71.8% and 621 + 1G greater than T 6.7%. We observed a significant difference between the Welsh and Scottish frequencies of 621 + 1G greater than T. To allow the rapid and efficient screening for the more common mutations we modified a multiplex used by Watson et al enabling the detection of delta F508, G551D, and R553X simultaneously with 621 + 1G greater than T. In parallel to this system we ran the Cellmark Diagnostics ARMS multiplex kit, which detects delta F508, 621 + 1G greater than T, G551D, and G542X. RFLP analysis of the 184 families shows that the delta F508 chromosomes are almost exclusively found on the B haplotype (XV2c 1, KM19 2); the other CF mutations have more heterogeneous backgrounds. Strong haplotype correlations exist between the markers XV2c, KM19, D9, and G2 and the other CF mutations. Haplotype data suggest that there are at least seven mutations that remain to be identified in these families.

Mild pulmonary disease in a cystic fibrosis child homozygous for R553X.

Nonsense mutations frequently cause severe illness because premature termination of messenger RNA translation usually creates un-stable truncated proteins. However, Cutting et al described two patients carrying nonsense mutations in each cystic fibrosis gene (G542X/ S1255X and R553X/W1316X) with severe pancreatic involvement but mild pulmonary disease. Furthermore, Cuppens et al and Bonduelle et al described children homozygous for the G542X stop mutation who were only mildly affected. Recently, Bal et a1 reported a patient homozygous for the R553X nonsense mutation who was moderately severely affected. We present the clinical and molecular findings of a child also homozygous for R553X but with mild pulmonary disease.

Development of an Antenatal Screening Programme for Congenital Abnormalities in a South Wales District: Lessons Learnt for Clinical Governance

An earlier report on antenatal screening for Down syndrome in a South Wales district identified sub-standard and variable practices. A multidisciplinary Professional Advisory Group was set up in 1996 to review the service and recommend a model of care, as well as quality outcome measures to form the standards for audit and evaluation. The programme drew heavily on evidence-based practice and the opinion and aspirations of the pregnant women. This was the first organised attempt at standardisation of the screening practices for congenital abnormalities in Wales. A year later, several goals had been achieved. Each obstetric unit now has a named Screening Midwife Specialist. The first genetic course in the UK specifically tailored for midwifes has been established. Lack of leadership in fetal medicine and ultrasound scanning was identified in one maternity unit, resulting in the appointment of two additional sonographers and a consultant obstetrician. The Professional Advisory Group produced a new, district-wide, annually updated information booklet for expectant mothers. A new information system was installed in each maternity unit to facilitate audit of outcome. Several clinical, biochemical and cytogenetic indicators were specified as quality outcome indicators and were collated and compared with the recommended standards. The uptake of serum screening has declined from around 95 to 75% in two units (to 62.9% overall, closely resembling the percentage expected based on the findings of a local survey of pregnant women). The rate of amniocentesis was significantly reduced by 28.7%, as women thought more clearly about their options and the limitations of tests. This suggests that women have a better understanding and more autonomy in making decisions regarding tests. An enthusiastic public health lead was essential in initiating and maintaining the changed programme.