Search PubMed⌕ Search

Biomedical subjects

J Burn

Publications and source records attributed to J Burn.

At least 109 records · Page 6Linked to original sources
PubMed1994

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗
PubMed1994

Relevance of the Human Genome Project to inherited metabolic disease.

The Human Genome Project is an international effort to identify the complete structure of the human genome. HUGO, the Human Genome Organization, facilitates international cooperation and exchange of information while the Genome Data Base will act as the on-line information retrieval and storage system for the huge amount of information being accumulated. The clinical register MIM (Mendelian Inheritance in Man) established by Victor McKusick is now an on-line resource that will allow biochemists working with inborn errors of metabolism to access the rapidly expanding body of knowledge. Biochemical and molecular genetics are complementary and should draw together to find solutions to the academic and clinical problems posed by inborn errors of metabolism.

Genetic Diseases, Inborn↗
PubMed1994

Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome.

The Muir-Torre syndrome, in which sebaceous gland tumours occur in association with internal malignancy, is inherited as an autosomal dominant disorder. Many features of the syndrome are similar to those of the Lynch II cancer family syndrome, and thus the two disorders might share a common genetic basis. We typed two large families with DNA markers on chromosome 2p around D2S123, a site recently shown to be linked to the Lynch II syndrome. LOD scores at this locus demonstrated significant and tight linkage to D2S123, suggesting that defects in the same gene might give rise to both syndromes.

Adult↗
PubMed1994

Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb.

Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date, the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and GABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA)n repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived from a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmid from this YAC clone falls within the deletion, suggesting that the minimal AS region is less than 200 kb. We also studied three loci within 15q11-13 which detect parent-of-origin specific DNA methylation imprints, and found that both normal maternal and paternal patterns were present in this patient.

Angelman Syndrome↗
PubMed1994

Natural history of trisomy 13.

The poor prognosis of patients with trisomy 13 has long been accepted and has been ascribed to brain and heart malformations. It has been suggested, however, that the long term survival is better than was previously thought and that cardiac surgery may be justified. This population based study reviews the incidence, antenatal diagnosis, spectrum of survival from congenital heart disease, and mode of death for patients with trisomy 13 in the Northern Health Region from 1985 to 1992. There was an observed prevalence at birth of 0.049/1000 live births and an expected prevalence, allowing for antenatal diagnosis, of 0.077. None of the cardiac lesions found would cause early death. The median survival in this series was four days; the longest survival was 3.5 months. The principal mode of death was apnoea in 14 of 16 children, irrespective of the presence of a cranial abnormality. In the light of these findings, cardiac surgery cannot be justified in patients with trisomy 13.

Adult↗
PubMed1994

Genetic heterogeneity in hereditary haemorrhagic telangiectasia.

A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are reported. All the previously reported 9q34 linked families contain at least one affected member with a symptomatic pulmonary arteriovenous malformation. We postulate that clinical heterogeneity may also be a feature of HHT with a significantly higher predisposition to symptomatic PAVMs associated with the HHT1 linked families.

Chromosome Mapping↗
PubMed1994

Meckel syndrome: what are the minimum diagnostic criteria?

Two sibs are described, the first of whom presented the classic Meckel syndrome triad of encephalocele, postaxial polydactyly, and characteristic renal cystic changes. The second sib had none of these abnormalities, but did show urethral atresia and preaxial polydactyly, two features previously described in some patients with Meckel syndrome. The two cases illustrate both the wide phenotypic spectrum of Meckel syndrome and the difficulty of attempting to define minimum diagnostic criteria for the disorder. The clinical implications arising from this problem are discussed.

Abnormalities, Multiple↗
PubMed1994

Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project.

BACKGROUND AND PURPOSE: There have been few community-based studies of long-term prognosis after acute stroke. This study aims to provide precise estimates of the absolute and relative risks of stroke recurrence in an unselected cohort of patients with a first-ever stroke. METHODS: Six hundred seventy-five patients were registered in a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed for up to 6.5 years. Their relative risk of recurrent stroke was calculated using age- and sex-specific incidence rates for first stroke in Oxfordshire. RESULTS: One hundred eighty recurrent episodes of stroke were identified, of which 135 were first recurrences. Given survival, the actuarial risk of suffering a recurrence was 30% (95% confidence interval, 20% to 39%) by 5 years, about nine times the risk of stroke in the general population. The risk was highest early after the first stroke: 13% (95% confidence interval, 10% to 16%) by 1 year, 15 times the risk in the general population. After the first year the average annual risk was about 4%. The risk of stroke recurrence did not appear to be related to age or pathological type of stroke. CONCLUSIONS: The absolute and relative risks of recurrent stroke are highest early after the first stroke but remain elevated for several years thereafter. Efforts at secondary prevention should be initiated as soon as possible and continued for several years to gain greatest benefit.

Actuarial Analysis↗
PubMed1994

Autosomal dominant transmission of Pallister-Hall syndrome.

A mother and daughter with Pallister-Hall syndrome are described. This documented parent-to-child transmission supports the hypothesis of autosomal dominant inheritance of this condition. The mother survived childhood and became pregnant without exogenous endocrine supplements, demonstrating that the gene manifests variable expressivity.

Adult↗
PubMed1993

Brachmann-de Lange syndrome. Delineation of the clinical phenotype.

A total of 31 cases previously diagnosed as having Brachmann-de Lange syndrome were ascertained and examined, of which 11 were thought to have been misdiagnosed. Of those correctly diagnosed, there appeared to be a phenotypic dichotomy with classical and mild cases. Those facial findings of greatest diagnostic value were the combination of the characteristic eyebrows, long philtrum, thin lips and crescent-shaped mouth. The characteristic eyebrows were neat, well defined and arched as though they had been pencilled. This combination of anomalies was absent in postpubertal males but not in postpubertal females. Facial abnormalities most likely to lead to incorrect use of the eponym were hypertrichosis, synophrys, and bushy eyebrows.

Adolescent↗
PubMed1993

Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11.

The velo-cardio-facial syndrome (VCFS) and DiGeorge sequence (DGS) have many similar phenotypic characteristics, suggesting that in some cases they share a common cause. DGS is known to be associated with monosomy for a region of chromosome 22q11, and DNA probes have been shown to detect these deletions even in patients with apparently normal chromosomes. Twelve patients with VCFS were examined and monosomy for a region of 22q11 was found in all patients. The DNA probes used in this study could not distinguish the VCFS locus and the DGS locus, indicating that the genes involved in these haploinsufficiencies are closely linked, and may be identical. The phenotypic variation of expression in VCFS and DGS may indicate that patients without the full spectrum of VCFS abnormalities but with some manifestations of the disorder may also have 22q11 deletions.

Abnormalities, Multiple↗
PubMed1993

The establishment of a polyposis register.

Guidelines are presented for the establishment of a regional or national register of patients with familial adenomatous polyposis. The detailed recommendations are based on the work in committees of the "Leeds Castle Polyposis Group" and the "EuroFAP". The aims of national and regional polyposis registers are discussed, and the stages of development of a register are reviewed: Ascertainment of probands, construction of pedigrees, identification of family members at risk, and screening of members at risk. The problem of data confidentiality is discussed.

Adenomatous Polyposis Coli↗