Biomedical subjects

John R W Yates

Publications and source records attributed to John R W Yates.

5 recordsLinked to original sources

PubMed2006

Tuberous sclerosis.

Tuberous sclerosis is a serious inherited disease which poses major challenges for affected families and those caring for them. Identification of the genes causing the condition and study of their protein products has shed light on the pathogenesis of the disease and provided valuable new information about signalling pathways regulating protein synthesis and cell growth. There is now the exciting possibility of drug therapy for some of the manifestations of the disease.

Adult↗

PubMed2006

Complement factor H variant Y402H is a major risk determinant for geographic atrophy and choroidal neovascularization in smokers and nonsmokers.

PURPOSE: The complement factor H (CFH) gene polymorphism Y402H (1277T-->C) has been associated with susceptibility to age-related macular degeneration (AMD). The purpose of this study was to confirm this association in a U.K. population, to determine whether the association holds for both geographic atrophy (GA) and choroidal neovascularization (CNV), and to investigate interactions with smoking. METHODS: A case-control study was undertaken in 443 cases of AMD, with 262 spouses as control subjects. All subjects completed a health and lifestyle questionnaire, had an ophthalmic assessment with fundus photography, and were genotyped. RESULTS: The frequencies of the C allele and CC genotype were significantly higher in cases than in controls. In comparison to the TT genotype, the odds ratios for AMD associated with the CT and CC genotypes were 3.1 (CI 2.0-4.6) and 6.3 (CI 3.8-10.4), respectively. The results were similar in subgroup analyses confined to cases with GA or CNV. The findings were also similar for subgroup analyses restricted to subjects who had never smoked, moderate smokers, or heavier smokers (>20 pack years of smoking). Heavier smokers with the CC genotype may be particularly at risk. The frequency of the CC genotype did not differ significantly between cases with and without a family history of AMD. There was no evidence that genotype had any influence on age at onset of disease. CONCLUSIONS: The CFH Y402H variant is strongly associated with both GA and CNV in the U.K. population. This association is similar in smokers and nonsmokers. Heavier smokers with the CC genotype may be at particular risk.

Aged↗

PubMed2004

Monozygotic twins with tuberous sclerosis discordant for the severity of developmental deficits.

A pair of monozygotic male twins with tuberous sclerosis (TS) were followed between 18 months and 3 years of age. Twin A with 25 large cortical tubers and hence extensive brain involvement was moderately mentally retarded and met criteria for autism. The other twin had more (n = 31) but smaller tubers. He was not mentally retarded and did not meet criteria for autism. This study provides evidence that nongenetic factors such as extent of brain abnormality and not just number of cortical tubers are important in determining phenotypic variability in TS. The findings also raise questions about the mechanisms giving rise to autism in TS.

Autistic Disorder↗

PubMed2003

Prevalence of mitral valve prolapse in Stickler syndrome.

The prevalence of mitral valve prolapse in Stickler syndrome has been reported to be much higher than in the general population. As a result, it has been recommended that all patients with Stickler syndrome undergo routine echocardiography and have antibiotic prophylaxis prior to surgery. The purpose of this study was to evaluate the prevalence of mitral valve prolapse in a large cohort of UK patients with Stickler syndrome in whom the clinical diagnosis has been confirmed by molecular genetic analysis. Probands and pedigrees were identified from the Vitreoretinal Service database according to previously published criteria. Ophthalmic, skeletal, audiometric, and orofacial features were assessed. Affected individuals underwent a full cardiological examination including auscultation and two-dimensional echocardiography. Mutation analysis of the COL2A1 and COL11A1 genes was carried out. Seventy-eight patients from 25 pedigrees were studied. Mutation analysis confirmed the clinical diagnosis in every pedigree. No patient was found to have clinical evidence of cardiovascular disease and no patient had significant mitral or other valvular prolapse on echocardiography. These data from a large cohort of UK patients with proven Stickler syndrome do not suggest an increased incidence of mitral valve prolapse over and above that found in the general population. Routine echocardiography screening and use of preoperative antibiotics are unnecessary and should be reserved for those individual cases where there is clear clinical indication.

Cohort Studies↗

PubMed2002

Nonsense-mediated RNA decay in the TSC1 gene suggests a useful tool pre- and post-positional cloning.

Many mRNAs carrying mutations that are predicted to encode a truncated protein are subject to a mechanism known as nonsense-mediated mRNA decay (NMD), which results in reduced levels of mutant transcript. Tuberous sclerosis (TSC), an autosomal dominant neurocutaneous disorder with mutations in either of two genes, TSC1 or TSC2, requires comprehensive screening of both genes for molecular diagnosis. Virtually all TSC1 mutations are predicted to truncate the protein product. Coding and newly identified 3' untranslated region polymorphisms in TSC1 were used to develop a transcript imbalance assay to investigate TSC1 transcript levels in patients. This approach allowed the correct identification of six out of seven TSC1 patients tested blind from a panel of TSC1 and TSC2 patients, with no false positives. The extent of NMD in TSC1 was found to correlate with each individual mutation regardless of intra-familial variation in clinical features and with no strong evidence for positional bias. NMD in TSC1 was more pronounced in cultured cells than in RNA prepared directly from peripheral lymphocytes (in which novel splicing of exon 5 was observed). The advent of a dense SNP map of transcribed regions of the genome may allow a similar transcript imbalance assay in the assessment of candidate genes for diseases whose causes are still unknown.

3' Untranslated Regions↗