Over 1,500 gene mutations are known to cause hypertrophic cardiomyopathy (HCM). Previous studies suggest that cardiac β-myosin heavy chain (MYH7) gene mutations are commonly associated with a more severe phenotype, compared to cardiac myosin binding protein-C (MYBPC3) gene mutations with milder phenotype, incomplete penetrance and later age of onset. Compound mutations can worsen the phenotype. This study aimed to validate these comparative differences in a large cohort of individuals and families with HCM. We performed genome-phenome correlation among 80 symptomatic HCM patients, 35 asymptomatic carriers and 35 non-carriers, using an 18-gene clinical diagnostic HCM panel. A total of 125 mutations were identified in 14 genes. MYBPC3 and MYH7 mutations contributed to 50.0% and 24.4% of the HCM patients, respectively, suggesting that MYBPC3 mutations were the most frequent cause of HCM in our cohort. Double mutations were found in only nine HCM patients (7.8%) who were phenotypically indistinguishable from single-mutation carriers. Comparisons of clinical parameters of MYBPC3 and MYH7 mutants were not statistically significant, but asymptomatic carriers had high left ventricular ejection fraction and diastolic dysfunction when compared to non-carriers. The presence of double mutations increases the risk for symptomatic HCM with no change in severity, as determined in this study subset. The pathologic effects of MYBPC3 and MYH7 were found to be independent of gene mutation location. Furthermore, HCM pathology is independent of protein domain disruption in both MYBPC3 and MYH7. These data provide evidence that MYBPC3 mutations constitute the preeminent cause of HCM and that they are phenotypically indistinguishable from HCM caused by MYH7 mutations.

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To understand the dynamic mechanisms governing soil-to-plant transfer of selenium (Se), technetium-99 ( 99 Tc) and iodine (I),, a pot experiment was undertaken using 30 contrasting soils after spiking with 77 Se, 99 Tc and 129 I, and incubating for 2.5 years. Two grass species (Agrostis capillaris and Lolium perenne) were grown under controlled conditions for 4 months with 3 cuts at approximately monthly intervals. Native (soil-derived) 78 Se and 127 I, as well as spiked 77 Se, 99 Tc and 129 I, were assayed in soil and plants by ICP-MS. The grasses exhibited similar behaviour with respect to uptake of all three elements. The greatest uptake observed was for 99 Tc, followed by 77 Se, with least uptake of 129 I, reflecting the transformations and interactions with soil of the three isotopes. Unlike soil-derived Se and I, the available pools of 77 Se, 99 Tc and 129 I were substantially depleted by plant uptake across the three cuts with lower concentrations observed in plant tissues in each subsequent cut. Comparison between total plant offtake and various soil species suggested that 77 SeO4 2-, 99 TcO4and 129 IO3 -, in soluble and adsorbed fractions were the most likely plant-available species. A greater ratio of 127 I/ 129 I in the soil solid phase compared to the solution phase confirmed incomplete mixing of spiked 129 I with native 127 I in the soil, despite the extended incubation period, leading to poor buffering of the spiked available pools. Compared to traditional expressions of soil-plant transfer factor (TFtotal), a transfer factor (TFavailable) expressed using volumetric concentrations of speciated 'available' fractions of each element showed little variation with soil properties.