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Biomedical subjects

E Bull

Publications and source records attributed to E Bull.

6 recordsLinked to original sources
PubMed2000

Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.

The Enzymatic Mutation Detection (EMDtrade mark) method is a streamlined and improved version of the original Enzymatic Cleavage of Mismatch (EMC) method. EMD is a fully homogeneous, rapid four step procedure that allows for detection and localization of mismatched or unmatched nucleotides within heteroduplex DNA. To test the utility of EMD for use in the screening of large and complex genes, the fibrillin 1 (FBN1) gene was scanned in a cohort of six patients diagnosed with connective tissue disorders. Four of the six patients were diagnosed with classic Marfan syndrome (MFS). The results were compared with a previous MDEtrade mark scanning of the same patient cohort. Two causative mutations, R565X and R1523X, were detected by EMD that were not detected by MDE. In both cases, the mutation resulted in premature termination of translation. In addition, several polymorphisms were detected by the enzymatic approach that failed detection by heteroduplex analysis. We propose that the EMD method is a sensitive and rapid approach to mutation detection in large genes such as FBN1.

Adult↗
PubMed1998

Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.

Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.

Adult↗
PubMed1995

Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.

Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS). This statement is supported by the observations that the classic Marfan phenotype cosegregates with intragenic and/or flanking marker alleles in all families tested and that a significant number of FBN1 mutations have been identified in affected individuals. We have now devised a method to screen the entire coding sequence and flanking splice junctions of FBN1. On completion for a panel of nine probands with classic MFS, six new mutations were identified that accounted for disease in seven (78%) of nine patients. Nine additional new mutations have been characterized in the early stages of a larger screening project. These 15 mutations were equally distributed throughout the gene and, with one exception, were specific to single families. One-third of mutations created premature termination codons, and 6 of 15 substituted residues with putative significance for calcium binding to epidermal growth factor (EGF)-like domains. Mutations causing severe and rapidly progressive disease that presents in the neonatal period can occur in a larger region of the gene than previously demonstrated, and the nature of the mutation is as important a determinant as its location, in predisposing to this phenotype.

Base Sequence↗
PubMed1991

Single-blind, randomised, parallel group study of the Bard Biocath catheter and a silicone elastomer coated catheter.

A group of 69 community patients undergoing long-term urethral catheterisation for urinary incontinence took part in this study; 33 patients with a mean age of 70.03 years (+/- 16.6) received the Dow Corning Silastic catheter (16 F 10-ml balloon) and 36 patients with a mean age of 75.61 years (+/- 12.6) received the Bard Biocath catheter (16 F 10-ml balloon). Over a 16-week period catheters were monitored every 2 weeks and changed as necessary. The Bard Biocath catheter remained in situ for an average of 89.61 days (+/- 35.31) and the Silastic catheter remained in situ for an average of 56.7 days (+/- 38.8); this difference was statistically significant. Used catheters were analysed for encrustation using scanning electron microscopy (SEM). The average time in situ for non-encrusted Biocath catheters was 83.7 days and 25.28 days for non-encrusted Silastic catheters. It was found that 70% of patients who received Biocath catheters preferred them to their previous catheters whereas only 30% of patients in the Silastic group preferred the trial catheter. The incidence of bypassing was 28% in the Biocath group and 52.8% in the Silastic group.

Aged↗