Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting

BackgroundMonogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension.MethodsWe performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays.Results21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%).ConclusionMolecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation.

Two-species hardcore reversible cellular automaton: matrix ansatz for dynamics and nonequilibrium stationary state

In this paper we study the statistical properties of a reversible cellular automaton in two out-of-equilibrium settings. In the first part we consider two instances of the initial value problem, corresponding to the inhomogeneous quench and the local quench. Our main result is an exact matrix product expression of the time evolution of the probability distribution, which we use to determine the time evolution of the density profiles analytically. In the second part we study the model on a finite lattice coupled with stochastic boundaries. Once again we derive an exact matrix product expression of the stationary distribution, as well as the particle current and density profiles in the stationary state. The exact expressions reveal the existence of different phases with either ballistic or diffusive transport depending on the boundary parameters.