BACKGROUND-Defects in the cardiac sodium channel gene, SCN5A, can cause a broad spectrum of inherited arrhythmia syndromes. After genotyping of a proband who presented with syncope, the SCN5A mutant P2006A and the common polymorphism H558R were identified.

Heterotrimeric G proteins, which consist of G , G and G subunits, function as molecular switches to regulate a wide range of developmental processes in plants. In this study, we characterize the function of rice RGG2, which encodes a type B G subunit, in grain size and yield production. The expression levels of RGG2 are significantly higher than those of other rice G -encoding genes in all tissues tested, suggesting that RGG2 plays essential roles in rice growth and development. By regulating cell expansion, RGG2 overexpression in Nipponbare (NIP) leads to reduced plant height and decreased grain size. By contrast, two mutants generated by the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) system in the Zhenshan 97 (ZS97) background, zrgg2-1 and zrgg2-2, exhibit enhanced growth, including elongated internodes, increased 1000-grain weight and plant biomass, and enhanced grain yield per plant (+11.8% and 16.0%, respectively). These results demonstrate that RGG2 acts as a negative regulator of plant growth and organ size in rice. By measuring the length of the second leaf sheath after gibberellin (GA ) treatment and the GA-induced α-amylase activity of seeds, we found that RGG2 is also involved in GA signaling. In summary, we propose that RGG2 may regulate grain and organ size via the GA pathway and that manipulation of RGG2 provides a novel strategy for rice grain yield enhancement. This article is protected by copyright. All rights reserved.

Background Brugada syndrome (BrS) is an arrhythmogenic disorder that has been linked to mutations in SCN5A, the gene encoding for the pore-forming α-subunit of the cardiac sodium channel. Typically, BrS mutations in SCN5A result in a reduction of sodium current with some mutations even exhibiting a dominant-negative effect on wild-type (WT) channels thus leading to an even more prominent decrease in current amplitudes. However, there is also a category of apparently benign (“atypical”) BrS SCN5A mutations that in vitro demonstrates only minor biophysical defects. It is therefore not clear how these mutations produce a BrS phenotype. We hypothesized that similar to dominant-negative mutations atypical mutations could lead to a reduction in sodium currents when co-expressed with WT to mimic the heterozygous patient genotype. Methods and Results WT and “atypical” BrS mutations were co-expressed in HEK293 cells, showing a reduction in sodium current densities similar to typical BrS mutations. Importantly, this reduction in sodium current was also seen when the atypical mutations were expressed in rat or human cardiomyocytes. This decrease in current density was the result of reduced surface expression of both mutant and WT channels. Conclusions Taken together, we have shown how apparently benign SCN5A BrS mutations can lead to the ECG abnormalities seen in BrS patients through an induced defect that is only present when the mutations are co-expressed with WT channels. Our work has implications for risk management and stratification for some SCN5A-implicated BrS patients.