A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy

<p>Abstract</p> <p>Background</p> <p>Calstabins 1 and 2 bind to Ryanodine receptors regulating muscle excitation-contraction coupling. Mutations in Ryanodine receptors affecting their interaction with calstabins lead to different cardiac pathologies. Animal studies suggest the involvement of calstabins with dilated cardiomyopathy.</p> <p>Results</p> <p>We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (<it>FKBP12 </it>and <it>FKBP12.6)</it>. No missense variant was found. Five no-coding variations were found but not related to the disease.</p> <p>Conclusions</p> <p>These data corroborate other studies suggesting that mutations in <it>FKBP12 </it>and <it>FKBP12.6 </it>genes are not commonly related to cardiac diseases.</p

Livelihood and vulnerability in the wake of Typhoon Yolanda: lessons of community and resilience

Livelihood strategies that are crafted in ‘extra-ordinary’ post-disaster conditions should also be able to function once some semblance of normalcy has resumed. This article aims to show that the vulnerability experienced in relation to Typhoon Yolanda was, and continues to be, directly linked to inadequate livelihood assets and opportunities. We examine the extent to which various livelihood strategies lessened vulnerability post-Typhoon Yolanda and argue that creating conditions under which disaster survivors have the freedom to pursue sustainable livelihood is essential in order to foster resilience and reduce vulnerability against future disasters. We offer suggestions to improve future relief efforts, including suggestions made by the survivors themselves. We caution against rehabilitation strategies that knowingly or unknowingly, resurrect pre-disaster vulnerability. Strategies that foster dependency, fail to appreciate local political or ecological conditions or undermine cooperation and cohesion in already vulnerable communities will be bound to fail. Some of the livelihood strategies that we observed post-Typhoon Yolanda failed on some or all of these points. It is important for future policy that these failings are addressed

Molecular cytogenetic analyses of breakpoints in apparently balanced reciprocal translocations carried by phenotypically normal individuals

To test the hypothesis that translocation breakpoints in normal individuals are simple and do not disrupt genes, we characterised the breakpoints in 13 phenotypically normal individuals incidentally ascertained with an apparently balanced reciprocal translocation. Cases were karyotyped, and the breakpoints were refined by fluorescence in situ hybridisation until breakpoint-spanning clones were identified. 1 Mb array-CGH was performed as a whole genome analysis tool to detect any imbalances in chromatin not directly involved in the breakpoints. Breakpoint-associated imbalances were not found in any of the patients analysed in this study. However, breakpoints which disrupted known genes were identified in two patients, with RYR2 disrupted in one patient and COL13A1 in the other. In a further eight patients, Ensembl mapping data suggested that a gene might be disrupted by a breakpoint. In one further patient, the translocation was shown to be nonreciprocal. This study shows that apparently balanced reciprocal translocations in phenotypically normal patients do not have imbalances at the breakpoints, in contrast to phenotypically abnormal patients where the translocation breakpoints are often associated with cryptic imbalances. However, phenotypically normal individuals, and phenotypically abnormal individuals may have genes disrupted and therefore inactivated by one of the breakpoints. The significance of these disruptions remains to be determined.<br/