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D J Brock

Publications and source records attributed to D J Brock.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cascade testing for the identification of carriers of cystic fibrosis.

It has been suggested that cascade testing, in which relatives of a person affected with cystic fibrosis (CF) are tested for carrier status, is preferable to screening individuals in the general population. This idea was examined by calculating the number of relatives requiring testing, assuming that it is necessary to identify all those of reproductive age no more distantly related to the proband than second cousins. Two hypothetical programmes were used, in each of which only blood relatives of an affected proband were tested and subsequent analysis applied to relatives of those with a positive result. If started in the grandparental generation, cascade testing of about 28 relatives for each proband would detect 86.4% of carriers in the family. If only carried out for the parental generation and their descendants, testing of about 35 relatives for each proband would detect 92.1% of carriers in the family. If cascade testing were restricted to the second cousin level, however, these programmes would only detect between 8 and 24% of all carrier couples. This contrasts with the 50% detection rate that has already been demonstrated for antenatal CF screening.

Cystic Fibrosis↗
PubMed1994

Heterogeneity analysis in 40 X-linked retinitis pigmentosa families.

Analysis of genetic heterogeneity in 40 kindreds with X-linked retinitis pigmentosa (XLRP), with 20 polymorphic markers, showed that significant heterogeneity is present (P = .001) and that 56% of kindreds are of RP3 type and that 26% are of RP2 type. The location of the RP3 locus was found to be 0.4 cM distal to OTC in the Xp21.1 region, and that of the RP2 locus was 6.5 cM proximal to DXS7 in Xp11.2-p11.3. Bayesian probabilities of linkage to RP2, RP3, or to neither locus were calculated. This showed that 20 of 40 kindreds could be assigned to one or the other locus, with a probability > .70 (14 kindreds with RP3 and 6 kindreds with RP2 disease). A further three kindreds were found to be unlinked to either locus, with a probability > .8. The remaining 17 kindreds could not be classified unambiguously. This highlights the difficulty of classifying families in the presence of genetic heterogeneity, where the two loci are separated by an estimated 16 cM.

Bayes Theorem↗
PubMed1994

Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within Xq27.3.

X-linked hydrocephalus is a well-defined disorder which accounts for > or = 7% of hydrocephalus in males. Pathologically, the condition is characterized by stenosis or obliteration of the aqueduct of Sylvius. Previous genetic linkage studies have suggested the likelihood of genetic homogeneity for this condition, with close linkage to the DXS52 and F8C markers in Xq28. We have investigated a family with typical X-linked aqueductal stenosis, in which no linkage to these markers was present. In this family, close linkage was established to the DXS548 and FRAXA loci in Xq27.3. Our findings demonstrate that X-linked aqueductal stenosis may result from mutations at two different loci on the X chromosome. Caution is indicated in using linkage for the prenatal diagnosis of X-linked hydrocephalus.

Cells, Cultured↗
PubMed1994

Mass screening for cystic fibrosis heterozygotes: two assay systems compared.

Two different assay systems were used to detect mutant cystic fibrosis alleles in mouthwash samples from pregnant women attending antenatal clinics. In the first phase of the study, comprising 3110 consecutive samples, we compared the performance of an in-house system and a commercial amplification refractory mutation system (ARMS). Successful analyses were completed at first attempt in approximately 90% of samples, and the patient resampling rate was 1.1%. There were no false positives and only one detected false negative. In the second phase, comprising 3333 consecutive samples, only ARMS was used. Again, there were no false positives and the patient resampling rate dropped to 0.5%. On the basis of convenience and reduced operator time, we have elected to use ARMS for further screening for cystic fibrosis heterozygotes.

Cystic Fibrosis↗
PubMed1993

Prenatal cystic fibrosis carrier screening: factors in a woman's decision to decline testing.

Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.

Abortion, Therapeutic↗
PubMed1993

Screening Alzheimer's disease patients for mutations in the amyloid precursor protein gene.

Over the past two years a series of different mutations has been discovered in the amyloid precursor protein (APP) gene in patients with Alzheimer's disease. All have been clustered in exons 16 and 17, a region encoding the beta A4 peptide found in the amyloid deposits of neuritic plaques and cerebral blood vessels. We have used the powerful technique of denaturing gradient gel electrophoresis to screen for mutations in exons 7, 16 and 17 of the APP gene in a cohort of 105 patients with presenile dementia of the Alzheimer type and 71 patients with autopsy-confirmed senile Alzheimer's disease. No new mutations were found, confirming earlier suggestions that APP mutations account for only a small proportion of cases of familial and sporadic Alzheimer's disease.

Adult↗
PubMed1993

A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes.

The Huntington's Disease (HD) Collaborative Research Group has recently published the sequence of a new cDNA, IT15, containing a polymorphic trinucleotide (CAG)n repeat that is expanded and unstable on HD chromosomes. There is a correlation between the repeat size and the age of onset of symptoms. The suggested polymerase chain reaction (PCR) assay of the (CAG)n repeat requires unusual reaction components and primer concentrations and the use of 5% polyacrylamide sequencing gels to resolve the amplification products. We present a simple PCR assay that produces a smaller product using standard reaction conditions. This gives better resolution of the (CAG)n expansion observed on HD chromosomes by acrylamide gel electrophoresis and allows sufficient product to be obtained to perform assays using agarose gels. This will allow diagnostic labs to do rapid and accurate presymptomatic testing of HD in high risk families.

Base Sequence↗
PubMed1993

Prenatal screening for cystic fibrosis: attitudes and responses of participants.

A screening programme to detect cystic fibrosis heterozygotes has been running in the antenatal clinics of a major Edinburgh maternity hospital for more than 2 years. A questionnaire was used to assess participants' knowledge of the genetics of the disorder and their attitudes to being screened. The respondents were 64 female heterozygotes and 63 of their non-heterozygous male partners, 101 female controls and 100 male controls. Although the two groups of controls received far less direct information than the carriers and their partners, all four groups were well informed about the genetics of cystic fibrosis and the significance of being a gene carrier. A majority of each group felt that adequate information had been given in the information leaflet, that they understood the purpose of screening and that they were glad to have participated. There was a consensus that CF carrier testing should be routinely offered to pregnant women, and also that it should be available in family planning clinics and GP health centres, but not in schools.

Attitude to Health↗
PubMed1993

A preliminary trial of couple screening for cystic fibrosis: designing an appropriate information leaflet.

An information leaflet, inviting participation in an antenatal screening trial for cystic fibrosis, was sent to 388 couples together with the pregnant woman's first clinic appointment. The leaflet pointed out that couples would be treated as a unit and that further action would be taken only if both partners were found to carry mutant alleles. Participants and non-participants were also asked to fill in a questionnaire eliciting their views on the leaflet. Three hundred and twelve (80%) questionnaires were returned and 253 (65%) couples elected to be screened. More than 90% of respondents found the leaflet easy to understand, although about 10% wanted more information on cystic fibrosis. The main reason for entering the trial was to avoid the birth of an affected child, and the main reason for non-entry was opposition to termination of pregnancy. There was little anxiety about the prospect of being screened. However, more than a third of couples mis-identified their risk of both carrying a CF gene, despite the figure of 1 in 600 being explicitly stated in the leaflet.

Comprehension↗
PubMed1993

A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.

Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.

Adult↗
PubMed1993

Prenatal screening for cystic fibrosis: psychological effects on carriers and their partners.

This study aimed to assess the psychological impact of screening for cystic fibrosis (CF) carrier status in a population of pregnant women. A cohort of 1798 women, who accepted the offer of testing before 18 weeks of pregnancy, filled in a self administered questionnaire seeking information on their perceived risk of carrier status and their emotional response, as well as a general health questionnaire (GHQ). Sixty-four women identified as CF carriers had partners who received a negative test result. This group and their partners were assessed, together with selected controls, on four further occasions: (1) on receiving the carrier's positive test result; (2) on receiving the partner's negative test result; (3) six weeks later; (4) six weeks after delivery. The instruments used were the GHQ and the Symptom Rating Test (SRT). When compared to control subjects, carriers showed a significant increase in generalised psychological disturbance which could be attributed specifically to symptoms of anxiety and depression during the period (average four days) that they awaited their partner's test result. On receiving a partner's negative test result, the carriers returned to control levels and maintained this equilibrium. Although there was no significant difference in generalised psychological disturbance between partners and their selected controls, partners did become significantly more anxious and manifested feelings of inadequacy while awaiting their own test result. Both male partners and male control subjects were more likely to become anxious if their partner was distressed.

Adolescent↗
PubMed1993

Presymptomatic testing for autosomal dominant spinocerebellar ataxia type 1.

Presymptomatic testing was done on four people from a large family in which an autosomal dominant form of spinocerebellar ataxia was segregating. Earlier genetic analysis had shown that in this family the disorder was tightly linked to an informative microsatellite polymorphism on chromosome 6p. Two subjects with prior risks of 50% of developing the disease had final risks after testing of 2%; the other two with prior risks of 25% had final risks of 1%. Chromosome 6p linked spinocerebellar ataxia may now be added to Huntington's disease as a late onset disorder in which genetic linkage may be used to carry out presymptomatic testing.

Adult↗