Reevaluation of the South Asian MYBPC3Δ25bp Intronic Deletion in Hypertrophic Cardiomyopathy.

BACKGROUND: The common intronic deletion, MYBPC3Δ25, detected in 4% to 8% of South Asian populations, is reported to be associated with cardiomyopathy, with ≈7-fold increased risk of disease in variant carriers. Here, we examine the contribution of MYBPC3Δ25 to hypertrophic cardiomyopathy (HCM) in a large patient cohort. METHODS: Sequence data from 2 HCM cohorts (n=5393) was analyzed to determine MYBPC3Δ25 frequency and co-occurrence of pathogenic variants in HCM genes. Case-control and haplotype analyses were performed to compare variant frequencies and assess disease association. Analyses were also undertaken to investigate the pathogenicity of a candidate variant MYBPC3 c.1224-52G>A. RESULTS: Our data suggest that the risk of HCM, previously attributed to MYBPC3Δ25, can be explained by enrichment of a derived haplotype, MYBPC3Δ25/-52, whereby a small subset of individuals bear both MYBPC3Δ25 and a rare pathogenic variant, MYBPC3 c.1224-52G>A. The intronic MYBPC3 c.1224-52G>A variant, which is not routinely evaluated by gene panel or exome sequencing, was detected in ≈1% of our HCM cohort. CONCLUSIONS: The MYBPC3 c.1224-52G>A variant explains the disease risk previously associated with MYBPC3Δ25 in the South Asian population and is one of the most frequent pathogenic variants in HCM in all populations; genotyping services should ensure coverage of this deep intronic mutation. Individuals carrying MYBPC3Δ25 alone are not at increased risk of HCM, and this variant should not be tested in isolation; this is important for the large majority of the 100 million individuals of South Asian ancestry who carry MYBPC3Δ25 and would previously have been declared at increased risk of HCM.

Fish species identification using PCR-RFLP analysis and lab-on-a-chip capillary electrophoresis: application to detect white fish species in food products and an interlaboratory study.

Identification of 10 white fish species associated with U.K. food products was achieved using PCR-RFLP of the mitochondrial cytochrome b gene. Use of lab-on-a-chip capillary electrophoresis for end-point analysis enabled accurate sizing of DNA fragments and identification of fish species at a level of 5% (w/w) in a fish admixture. One restriction enzyme, DdeI, allowed discrimination of eight species. When combined with NlaIII and HaeIII, specific profiles for all 10 species were generated. The method was applied to a range of products and subjected to an interlaboratory study carried out by five U.K. food control laboratories. One hundred percent correct identification of single species samples and six of nine admixture samples was achieved by all laboratories. The results indicated that fish species identification could be carried out using a database of PCR-RFLP profiles without the need for reference materials.

A comparison of attitudes and practices of gutka users and non-users in Chitrakoot, India. A pilot.

AIMS AND OBJECTIVES: As part of a student elective, this pilot study aimed at investigating attitudes and practices concerning gutka use in a town in India. It was hoped that information gained would assist in formulating an appropriate health education programme to encourage gutka cessation locally and would provide more information about a habit which is also relevant to some UK South Asian populations. DESIGN AND SETTING: 124 consecutively attending subjects (103 males and 21 females) at a charity-run dental clinic in Chitrakoot, India, were interviewed using a semi-structured questionnaire. MAIN FINDINGS: 57 (46%) of the respondents, of whom there were more males than females (103 v. 21), reported current gutka use. There were no differences between users and non-users by age or educational attainment. Users found gutka 'helpful' in relieving tension, aiding con- centration, combating bad breath and as a leisure activity. They all cited other family members who were using gutka as compared to only 40% of the gutka non-users. Cancer was mentioned as a harmful outcome of gutka use more frequently by non-users. Of the 57 gutka chewers, 36 also chewed paan with tobacco and 20 smoked cigarettes. CONCLUSIONS: Gutka chewing involved almost half of the study population and proportionately more males than females. The habit was endemic within families. Many gutka chewers also smoked, chewed paan or drank alcohol, representing a high-risk behaviour for oral cancer. Proportionately more non-chewers were aware of the link with cancer. There are clear implications for health promotion in India. General dental practitioners in the UK should also be aware of the possibility that this habit is becoming more widely adopted in South Asian communities here, involving young children as well as adults. Research into gutka use is also required in the UK.