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Biomedical subjects

J Burn

Publications and source records attributed to J Burn.

At least 73 records · Page 4Linked to original sources
PubMed1997

Maternal serum screening for Down's syndrome: a survey of midwives' views.

The lack of consensus regarding the implementation of maternal serum screening, has led to a widespread variation in practice. The importance of the role of midwives within the service has been recognised. All maternity units in the Northern region now have a designated 'co-ordinator' in an attempt to improve service delivery, professional liaison and training. This study was designed to obtain midwives' views about maternal serum screening in principle and to assess whether any changes had occurred since the introduction of co-ordinators. Semi-structured, postal questionnaires were sent to all midwives in one health authority for them to complete and return. Within this authority, one maternity unit offered universal screening whereas the other maintained a selective policy. Responses were obtained from 90 out of 133 (67.7%). There was almost unanimous support for the principle of screening 86 out of 90 (95.5%) and most midwives considered the offer of screening should be an NHS service, independent of age 78 out of 90 (86.7%). Half of the respondents 46 out of 90 (51.2%) reported that the introduction of a co-ordinator had been successful in improving staff education but requests for further training and updating were made by 69 out of 90 (76.6%) despite having had this organized training input: although those midwives who were regularly involved with screening made significantly fewer requests 27 out of 45 (60%). These findings confirmed our previous recommendation that ongoing responsibility for such provision would be required. The results of the study provided a useful contribution towards the review of screening policy undertaken by the health authority, as well as evidence upon which to base further development of the role of the co-ordinators in their support of midwives.

Attitude of Health Personnel↗
PubMed1997

Cancer risk associated with germline DNA mismatch repair gene mutations.

The autosomal dominant syndrome of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is due to germline DNA mismatch repair gene mutations in most cases. However, the penetrance of such mutations outwith classical HNPCC kindreds is unknown because families studied to date have been specifically selected for research purposes. Using a population-based strategy, we have calculated the lifetime cancer risk associated with germline DNA mismatch repair gene mutations, irrespective of their family history. We identified 67 gene carriers whose risk to age 70 for all cancers was 91% for males and 69% for females. The risk of developing colorectal cancer was significantly greater for males than for females (74% versus 30%, P= 0.006). The risk of uterine cancer (42%) exceeded that for colorectal cancer in females, emphasising the need for uterine screening. Our findings give further insight into the biological effect of defective DNA mismatch repair. We have demonstrated a systematic approach to identifying individuals at high risk of cancer but who may not be part of classical HNPCC families. The risk estimates derived from these analyses provide a rational basis on which to guide genetic counselling and to tailor clinical surveillance.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1997

Strategies for antenatal detection of Down's syndrome.

AIM: To predict the effect of maternal serum screening and fetal echocardiography on the birth prevalence of Down's syndrome. METHODS: The outcome of all Down's syndrome pregnancies in the Northern Health Region between 1985 and 1991 was retrospectively ascertained. The number and outcome of all Down's syndrome pregnancies were used to define a theoretical population which would exist in the absence of screening. Published reports were used to predict the effects of screening strategies. RESULTS: Down's syndrome was identified in 412 pregnancies of which 315 (76%) resulted in live birth. A theoretical population with no antenatal screening would be expected to produce 31 stillbirths and 381 (92%) live births affected by Down's syndrome. In the same population a programme of maternal serum screening and fetal echocardiography would lead to 155 and 14 terminations, respectively, and when combined, would reduce affected live births to 229 (56%). CONCLUSIONS: Even if maternal serum screening and fetal echocardiography achieve their predicted potential, around half of all pregnancies affected by Down's syndrome will result in live born babies.

Adult↗
PubMed1997

Absence of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy.

OBJECTIVE: To determine the frequency of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy. DESIGN: Mutation screening of the terminal 200 base pairs of connexin43 gene coding sequence in a series of patients from tertiary care centres. PATIENTS: 48 patients with visceroatrial heterotaxy attending UK Regional Paediatric Cardiology Centres. RESULTS: No changes from the published connexin43 consensus sequence were found in any of the 48 patients studied. CONCLUSIONS: Germline mutations of the phosphorylation sites in teh regulatory domain of the connexin43 gene are rare in patients with visceroatrial heterotaxy.

Base Sequence↗
PubMed1997

Large scale deletions in the GPC3 gene may account for a minority of cases of Simpson-Golabi-Behmel syndrome.

AIMS OF THE STUDY: To identify the proportion and type of deletions present in the glypican 3 (GPC3) gene in a group of patients with Simpson-Golabi-Behmel syndrome (SGBS). SUBJECTS AND METHODS: PCR analysis using primer pairs which amplify fragments from each of the eight exons of the GPC3 gene was carried out in a series of 18 families with SGBS (approximately half of reported cases). RESULTS: Deletions were detected in only five families (one reported previously). We found deletions in all exons of the gene except exon 3. CONCLUSIONS: Our results suggest that large scale deletions may be less common in SGBS than was originally thought. One patient, with an exon 4 and 5 deletion, lacked the characteristic facial dysmorphic features. This raises the possibility of involvement of GPC3 gene defects in a wider range of overgrowth disorders.

Abnormalities, Multiple↗
PubMed1997

Endoscopic screening and surgery for familial adenomatous polyposis: dangerous delays.

BACKGROUND: Registries for patients with familial adenomatous polyposis (FAP) can improve patient management. However, in relation to colorectal cancer, a critical review has not previously been undertaken of the effectiveness of screening and surgical protocols within a registry. METHODS: A review was undertaken of 63 gene carriers who received primary treatment for FAP between 1987, when the Northern Region Polyposis Registry was formed, and 1995. RESULTS: In some gene carriers with colorectal cancer, surgery was delayed because of social factors or unpleasant surgical experiences in the family. Colonoscopy failed to detect five colorectal cancers. CONCLUSIONS: Delays in treatment still occur in patients with FAP and colorectal cancer, often because of complex social problems and patients' fear of surgery. If multiple colorectal polyps are present, colonoscopy is not a reliable screening test for malignancy and prophylactic surgery is indicated, preferably before the patient is 20 years old.

Adenomatous Polyposis Coli↗
PubMed1996

The cylindromatosis gene (cyld1) on chromosome 16q may be the only tumour suppressor gene involved in the development of cylindromas.

Hereditary cylindromatosis is a rare autosomal dominant disease characterised by the development of multiple benign neoplasms of the skin. We recently localised the gene responsible for this disease (cyld1) to chromosome 16q12-q13 and provided evidence that it is a tumour suppressor gene (Biggs et al., 1995). We have now examined polymorphic markers on every chromosome, some of which are close to known tumour suppressor genes, in 25 tumours from 4 individuals with familial cylindromatosis. No loss of heterozygosity (LOH) was detected other than at loci on chromosome 16q. This observation suggests that the cyld1 gene may be the only tumour suppressor gene implicated in the development of cylindromas. We have also demonstrated LOH using markers on chromosome 16q in 8/14 (57%) sporadic cylindromas, indicating that the cyld1 gene is likely to be involved in the genesis of both familial and sporadic cylindromas.

Carcinoma, Adenoid Cystic↗
PubMed1996

X-inactivation patterns in monozygotic and dizygotic female twins.

We have tested the hypothesis that contrasting X-inactivation patterns could be a trigger for monozygotic twinning in females. X-inactivation patterns were studied in umbilical cord tissue in 43 monozygotic twin pairs and 24 dizygotic twin pairs. Very skewed or non-random X-inactivation patterns were observed in both twins in six of the monozygotic twin pairs and in one of the dizygotic twin pairs. Contrasting X-inactivation patterns occurred in only one of the six monozygotic twin pairs. This does not support the original hypothesis. There is a trend to extreme skewing of X-inactivation pattern occurring more frequently in monozygotic twins.

Base Sequence↗
PubMed1996

Mutation detection in exons 1-14 of the adenomatous polyposis coli gene: identification of an alternatively spliced transcript.

Mutations in the APC gene are responsible for the dominantly inherited colon cancer syndrome, familial adenomatous polyposis (FAP). We have designed PCR primers which allow amplification by RT-PCR of exons 1-14 of the APC gene in six overlapping segments. The amplicons have been screened for the presence of mutations in patients affected with FAP using heteroduplex analysis. One patient has been identified with an alternatively spliced transcript involving exon 14 and a single base insertion mutation within the same exon.

Alternative Splicing↗
PubMed1996

Developmental genetics of the heart.

Studies of children with heart defects and chromosomal anomalies have led to the discovery that loss of an elastin gene can cause supravalvar aortic stenosis and that a 2 Mb deletion from 22q11 is second only to Down's syndrome as a cause of heart defects. Molecular dissection of the 22q11 region to find the genes which produce the outflow-tract defects and other disorders of neural crest migration has proven more difficult, as there are a large number of genes in the deleted region. Classic mapping studies have located a gene which can cause total anomalous venous drainage near the centromere of chromosome 4. Knockout mouse studies have demonstrated an important role in cardiac development for, amongst others, endothelin-1 and neuregulin. Functional redundancy and maternal rescue are two reasons why knockouts do not always live up to our expectations. Serendipitous findings in the mouse are equally important. Work continues to isolate the inversion of embryo turning (inv) gene which invariably disturb the left-->right gradient in homozygotes, causing heart defects in many instances. Sadly, the original insertional mutation has resulted in a complex deletion duplication which has slowed discovery of the coding sequence.

Animals↗
PubMed1996

Genetic mapping of the human homologue (T) of mouse T(Brachyury) and a search for allele association between human T and spina bifida.

We describe a genetic analysis of the human homologue (T) of the mouse T (Brachyury) gene; human T was recently cloned in our laboratory. The protein product of the T gene is a transcription factor crucial in vertebrates for the formation of normal mesoderm. T mutant Brachyury mice die in midgestation with severe defects in posterior mesodermal tissues; heterozygous mice are viable but have posterior axial malformations. In addition to its importance in development, T has intrigued geneticists because of its association with the mouse t-haplotype; this haplotype is a variant form of the t-complex and is characterized by transmission ratio distortion, male sterility and recombination suppression. We have identified a common polymorphism of human T by single strand conformation polymorphism (SSCP) and used this in mapping studies and to re-investigate the idea that human T is involved in susceptibility to the multifactorial, neural tube defect, spina bifida. Our mapping data show that human T maps to 6q27 and lies between two other genes of the t-complex, TCP1 and TCP10. These data add to the evidence that in man the genes of the t-complex are split into two main locations on the short and long arms of chromosome 6. We have used an allele association test which is independent of mode of inheritance and penetrance to analyse data from the spina bifida families. Using this test we find evidence for a significant (p = 0.02) association between transmission of the TIVS7-2 allele of the human T gene and spina bifida.

Alleles↗
PubMed1996

Further evidence of genetic heterogeneity in hereditary hydronephrosis.

Hereditary hydronephrosis is a rare condition but several families are described in the literature. The inheritance pattern is autosomal dominant (McKusick number 143400) but the exact aetiology of the hydronephrosis is not clear. However, linkage with the HLA region on chromosome six has been shown previously. We report a family not showing linkage to this region, giving further evidence of genetic heterogeneity in this condition.

Adolescent↗
PubMed1996

Co-dominant inheritance of hyperekplexia and spastic paraparesis.

In four generations of a family with autosomal dominant hyperekplexia (startle disease), untreated affected adult members had pes cavus and extensor plantar responses, as well as hyper-reflexia. Electroencephalography during a startle, electromyography, nerve conduction velocities and somatosensory evoked potentials were normal. Genetic studies showed linkage to the CSF1R locus on chromosome 5q33-q35, which includes the glycine receptor. This either represents a variant of hyperekplexia with spasticity or suggests that genes for hyperekplexia and a form of hereditary spastic paraparesis may be closely linked.

Adult↗