Search PubMed⌕ Search

Biomedical subjects

D J Brock

Publications and source records attributed to D J Brock.

At least 37 records · Page 2Linked to original sources
PubMed1995

A single-tube multiplex system for the simultaneous detection of 10 common cystic fibrosis mutations.

We describe a nonisotopic single-tube polymerase chain reaction (PCR) multiplex system that detects 10 of the more common cystic fibrosis (CF) mutations (delta F508, delta I507, V520F, G551D, G542X, R553X, R117H, 621 + 1G-->T, N1303K, A455E). The use of this method detects approximately 90% of the CF alleles in the British population. Five exons of the CF gene are amplified simultaneously by PCR, followed by an overnight triple enzyme restriction digest, and then resolved by high-resolution gel acrylamide electrophoresis.

Base Sequence↗
PubMed1995

Huntington's disease in a Sudanese family from Khartoum.

Typical Huntington's disease (HD) was studied in a 40-year-old Sudanese man from Khartoum. He had 51 CAG repeats in the Huntington's gene. It is suspected that his mother and his 16-year-old son (both deceased) were also affected. Up to now, there had only been anecdotal evidence of HD in the Sudanese.

Adult↗
PubMed1995

Carrier screening in the community.

A number of different models of cystic fibrosis (CF) carrier screening have now been tested in pilot trials. Apart from opportunistic and cascade testing (which are strictly speaking not true forms of screening), the major programmes have been directed either to young adults in primary care or to pregnant women in antenatal clinics. Only in the latter form of screening has sufficient data been collected to allow conclusions to be reached on the optimum mode of delivery. It seems very probable that when CF carrier screening passes into routine service, it will be the antenatal couple model that is used.

Adult↗
PubMed1995

Superoxide dismutase mutations in an unselected cohort of Scottish amyotrophic lateral sclerosis patients.

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are responsible for some cases of familial amyotrophic lateral sclerosis (ALS). We have shown that SOD1 mutations can also occur in apparently sporadic ALS. To establish how often this happens we have undertaken a study of the prevalence of SOD1 mutations in an unselected cohort of Scottish ALS patients, with both sporadic (n = 57) and familial (n = 10) disease. Single strand conformation polymorphism analysis was used to scan for new mutations, and selective restriction enzyme digestion to screen for 11 of the 20 SOD1 mutations published to date. We detected mutations in five (50%) of the familial ALS patients and also in four (7%) of the sporadic patients. One mutation, ile113thr, seems to be particularly prevalent in the Scottish population since it was detected in a total of 6/67 (9%) unrelated cases.

Aged↗
PubMed1995

Heterozygote screening for cystic fibrosis.

In the 5 years since the cloning of the cystic fibrosis (CF) gene, several experimental trials of CF carrier screening have been performed and reported. Two particular groups have been targetted: young adults near reproductive age, and pregnant women. The three trials directed at young adults have shown that the method of presentation is a major determinant of take-up rates; an offer of screening by personal intervention gives high acceptance while an offer by mail or leaflet produces disappointing results. There is a strong suggestion that screening is being foisted on an unreceptive group, whose response is one of politeness rather than conviction--'supply push' rather than 'demand pull'. Trials of screening during pregnancy have been more extensive and more satisfactory. Two models have been tested. In sequential delivery, women are screened first and their partners only tested when they are found positive for CF alleles. This can lead to anxiety, during the period while positive women await their partner's result. In couple screening both partners agree to be treated as a unit and reported as high risk only when both are positive. In other situations they are regarded as negative. Couple screening has turned out to be remarkably efficient, trouble-free and consumer-friendly, and has become the method of choice for integration into routine health care.

Cystic Fibrosis↗
PubMed1994

Antenatal screening for cystic fibrosis: a trial of the couple model.

OBJECTIVE: To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. DESIGN: Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. SETTING: Two large maternity hospitals in Edinburgh. SUBJECTS: Screening was offered to all couples who booked at one of the two hospitals. MAIN OUTCOME MEASURES: (a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. RESULTS: Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive--that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. CONCLUSIONS: Antenatal couple screening is a satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.

Anxiety↗
PubMed1994

Gene therapy for cystic fibrosis: will it affect the uptake of prenatal carrier screening?

We report a study which examined whether the decision of 135 couples to accept prenatal cystic fibrosis (CF) carrier screening would be influenced by the advent of gene therapy. A majority (91 couples; 67 per cent) felt that gene therapy for CF would not influence their decision to be screened. Twenty-two couples (16 per cent) stated that they would decline to be screened and an equal number felt ambivalent. Even if the life expectancy of a CF sufferer were increased by gene therapy to normal, 78 per cent of couples would still wish to avail themselves of prenatal carrier screening. A majority of women who decline screening do so because they are opposed to termination of pregnancy. The availability of gene therapy could increase the proportion of couples who accept screening.

Cystic Fibrosis↗
PubMed1994

Carrier screening for cystic fibrosis.

A number of different models of CF carrier screening have now been tested in pilot trials. Apart from opportunistic and cascade testing (which are strictly speaking not true forms of screening), the major programmes have been directed either to young adults in primary care or to pregnant women in antenatal clinics. Only in the latter form of screening has sufficient data been collected to allow conclusions to be reached on the optimum mode of delivery. It seems very probable that when CF carrier screening passes into routine service, it will be the antenatal couple model that is used.

Cystic Fibrosis↗
PubMed1994

Use of stable dye-DNA intercalating complexes to detect cystic fibrosis mutations.

Several dyes are now known which intercalate into double-stranded DNA with fluorescence enhancement. One such is TOTO (1,1'-(4,4,7,7-tetramethyl-4,7-diazaundecamethylene)-bis-4-[3-meth yl-2,3- dihydro-(benzo-1,3-thiazole)-2-methlyidene]-quinolinium tetraiodide), a homodimer of thiazole orange, whose complexes with DNA are stable to electrophoresis and show a 1000-fold enhancement after binding. We demonstrate that this reagent can be successfully used in combination with a laser-excited fluorescence gel scanner to detect the three most common cystic fibrosis mutant alleles, delta F508, G551D and G542X. This has potential application to mass population heterozygote screening.

Alleles↗
PubMed1994

A novel mutation in the fibrillin gene (FBN1) in familial arachnodactyly.

Mutations of the fibrillin gene (FBN1) are known to cause classical Marfan's syndrome, ectopia lentis and neonatal Marfan's syndrome. We have identified a novel missense mutation in exon 28 of the FBN1 gene (R1170H) which is responsible for an atypical marfanoid phenotype characterised by dolichostenomelia and arachnodactyly.

Adult↗
PubMed1994

Identification of a novel exon 4 SOD1 mutation in a sporadic amyotrophic lateral sclerosis patient.

We have been screening a cohort of 46 sporadic and 10 familial amyotrophic lateral sclerosis patients for mutations in the superoxide dismutase gene (SOD1) using a combination of SSCP and direct PCR sequencing. A novel missense mutation (Asp101Asn) has been detected in one sporadic patient and a previously reported mutation has been found in two familial cases.

Amyotrophic Lateral Sclerosis↗
PubMed1994

A single allele from the polymorphic CCG rich sequence immediately 3' to the unstable CAG trinucleotide in the IT15 cDNA shows almost complete disequilibrium with Huntington's disease chromosomes in the Scottish population.

The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and have found very strong evidence for disequilibrium in this population. For the 131 families where phase was unambiguously determined, 130 were shown to have a CCG repeat allele of 176 bp cosegregating with the HD chromosome. This observation is significantly different to the normal population distribution where 31% of people have an allele of 185 bp. The evidence for and against a possible founder effect in the Scottish HD population is discussed. We propose the hypothesis that we may have identified a region of the IT15 gene that is critical in Huntington's disease.

Alleles↗