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Biomedical subjects

N P Burrows

Publications and source records attributed to N P Burrows.

At least 19 recordsLinked to original sources
PubMed2004

Case 1.

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Female↗
PubMed2003

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗
PubMed2003

Woody hands.

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Cystadenocarcinoma, Papillary↗
PubMed2003

Short-term growth and bone turnover in children undergoing occlusive steroid ('Wet-Wrap') dressings for treatment of atopic eczema.

To assess the effects of steroid wet-wrap therapy on short-term growth and bone turnover, eight prepubertal (M:F,5:3) children with a median age of 5.1years (range 3.3-8.8) were studied over a 2-week period prior to therapy and at 2-week intervals during therapy. Short-term growth was assessed by measuring lower leg length velocity (LLLV) by knemometry and bone and collagen turnover was assessed by urinary deoxypyridinoline crosslink excretion corrected for creatinine excretion (DPD). Median duration of study during occlusive dressings was 12 weeks (range 2-18). Topical beclomethasone dipropionate diluted 1:10 or 1:4 in white soft paraffin was applied under tubular (Tubifast) bandages in 7/8 children. Median LLLV before and during therapy were 0.43 mm/week (10(th),90(th) centile; 0.0,0.7) and 0.42 mm/week (10(th),90(th) centile; -0.35,1.01), respectively (not significant). Median DPD before and during therapy were 25.9 nmol/l/creatinine (10(th),90(th) centile; 20.8, 33.0) and 26.3 nmol/l/creatinine (10(th),90(th) centile; 21.7, 34.1) respectively (not significant). Non-invasive assessment of the effects of steroid wet-wrap therapy can be performed in children with eczema. These preliminary results show no substantial growth promoting or adverse effects of therapy.

Bone Remodeling↗
PubMed2001

Dissecting folliculitis of the scalp with marginal keratitis.

We describe a young man with dissecting folliculitis of the scalp, who subsequently developed marginal keratitis. We are unaware of any previous reports of this association. The aetiology of dissecting folliculitis is thought to relate to abnormal follicular occlusion with subsequent suppuration, although an infective process has never been established. Marginal keratitis is postulated, but not proven, to be caused by an enhanced immune response to Staphylococcus aureus antigens. We suggest that a similar abnormal response to infection may be important in these two conditions. This case also highlights ocular complications which may occur in patients with dissecting folliculitis.

Administration, Topical↗
PubMed2001

Elastosis perforans serpiginosa and associated disorders.

We report elastosis perforans serpiginosa (EPS) arising in three patients with Ehlers-Danlos syndrome, osteogenesis imperfecta and Down's syndrome. These cases illustrate some of the rare but well-recognized disease associations with EPS. The other causes of EPS are reviewed.

Adolescent↗
PubMed2000

Dispersal of radioisotope labelled solution following deep dermal injection in Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is the commonest inherited disorder of connective tissue, affecting around 10 000 patients in the UK. Patients with EDS have reported that local anaesthetic is often ineffective. Patients with less severe skin laxity often have the most problems. We have postulated that this resistance to local anaesthetics is not due to the lax connective tissues as is often assumed. This study used radioactively labelled solution ((99m)Tc-pertechnetate) administered as a deep dermal injection in the forearm. The rate of dispersal of isotope was measured over 60 min and found to be identical between six patients with EDS and three controls. The effects of local anaesthetics are complex and depend on the individual chemical properties of the agent and a number of tissue factors. This study would suggest that the lack of effectiveness of local anaesthetic solutions is not due to rapid dispersal of solution. It is unlikely therefore that its lack of effect can be compensated for by simply increasing the amount used. The diagnosis of EDS should be considered in any patient who complains unexpectedly of pain during their procedure, particularly when the surgeon knows that an adequate volume of local anaesthetic has been used.

Administration, Cutaneous↗
PubMed1999

The molecular genetics of the Ehlers-Danlos syndrome.

The identification and investigation of many inherited disorders has an importance out of proportion to their frequency because of the insights they provide into physiological, pathological and molecular mechanisms. This is true of the heritable disorders of connective tissue which are a diverse group of conditions involving cutaneous, musculoskeletal, cardiovascular, ocular, gastrointestinal and pulmonary systems. The Ehlers-Danlos syndrome (EDS), which shows great clinical variability and genetic heterogeneity, is one example which has particular relevance to the dermatologist and is the focus of this review.

Collagen↗
PubMed1998

A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families.

Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective-tissue disorders characterized by skin fragility, joint laxity, and skeletal deformities. Type V collagen appears to have a causal role in EDS types I and II, which show phenotypic overlap and may sometimes be allelic. Type V collagen can exist as a heterotrimer, [alpha1(V)]2alpha2(V), and it both coassembles with and regulates type I collagen-fibril diameter. Using an intragenic COL5A1 polymorphism, we have demonstrated linkage, at zero recombination, to the same allele in two large British EDS type II families (LOD scores 4.1 and 4.3). Affected members from each family were heterozygous for a point mutation in intron 32 (IVS32:T-25G), causing the 45-bp exon 33 to be lost from the mRNA in approximately 60% of transcripts from the mutant gene. This mutation lies only 2 bp upstream of a highly conserved adenosine in the consensus branch-site sequence, which is required for lariat formation. Although both families shared the same marker allele, we have been unable to identify a common genealogy. This is the first description of a mutation at the lariat branch site, which plays a pivotal role in the splicing mechanism, in a collagen gene. Very probably, the resulting in-frame exon skip has a dominant-negative effect due to incorporation of the mutant proalpha chain into the triple-helical molecule. These findings further confirm the importance of type V collagen in the causation of EDS type II, and the novel collagen mutation indicates the importance of the lariat branch site in splicing.

Alternative Splicing↗