AimWe report diverse phenotypic consequences of the delQKP-1507–1509 cardiac sodium channel mutation in three generations of a Chinese family.Methods and resultsClinical and electrocardiographic (ECG), echocardiographic examination was followed by direct sequencing of SCN5A, KCNQ1, HERG, and LAMIN A/C to screen genomic DNA from blood samples. Of two mutation carriers, the proband was born with conduction disorders including second-degree atrioventricular (AV) block with prolonged QTc interval, additionally showing left anterior fascicular block (LAFB), incomplete right bundle-branch block (IRBBB), and intermittent third-degree AV block at 2 years, and clinical presentations of multiple syncope despite normal electroencephalograms at 8 years. Continuous ECG monitoring following presentation at 13 years revealed prolonged QTc and biphasic T-waves, multiple episodes of ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Transthoracal echocardiography then revealed left ventricular dilatation and reduced systolic function. Another mutation carrier showed features of long QT syndrome type 3 (LQT3), LAFB, and dilated cardiomyopathy (DCM). Two additional subjects died suddenly at 13 and 33 years.ConclusionThis data compliments and expands the spectrum of phenotypes resulting from this known gain-of-function mutation, including not only LQT3, cardiac conduction defects, and sudden death but also DCM, hitherto associated with loss-of-function mutations, for the first time.

Sequencing of the KCNQ2 gene revealed that all 17 affected family members carried a heterozygous Gly-to-Val (G271V) mutation in the conserved pore region that resulted from a guanine-to-thymine transition in exon 5 of KCNQ2. The same mutation with a comparable localization in the KCNQ3 (G310V) gene has been found in BFNS patients. The same conserved amino acid was also found to be mutated in the KCNQ1 gene in a family with Long QT Syndrome.

According to historical records, ethnic Hui in China obtained substantial genetic components from western Eurasian populations during their Islamization. However, some scholars believed that the ancestry of Hui people were native Chinese populations. In this context, the formation of Hui is due to simple cultural diffusion rather than demic diffusion. In this study, we examined the forensic and population genetic application of the 30 InDel loci in Hui population from Ningxia Hui Autonomous Region, Northwest China. Genotype analysis of 129 unrelated individuals revealed that all loci were in the Hardy–Weinberg equilibrium in Ningxia Hui. Forensic indices calculated from genotypes demonstrated that this panel, Qiagen DIPplex ® Investigator kit, was powerful enough to be used in individual identification but not in paternity cases. Through population genetic analysis, we found that Ningxia Hui received much more genetic contributions from East Asian populations than those from western Eurasian populations. Finally, we statistically identified the admixture signal of eastern and western Eurasians, although the latter is weak, in Ningxia Hui via the three-population test. All this evidence suggested that the formation of Ningxia Hui was mainly attributed to the cultural transformation of local Chinese residents with minor gene flow from western Eurasian populations.

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This study aimed to explore the effect of the TSLP-DC-OX40L pathway in asthma pathogenesis and airway inflammation in mice. For this, 65 male BALF/c mice were distributed among the control, asthma, immunoglobulin G (IgG) + asthma (IgG, 500 μg/500 μL, intratracheal injection of 50 μL each time), LY294002 (OX40L inhibitor) + asthma (intratracheal injection of 2 mg/kg LY294002), and anti-TSLP + asthma (intratracheal injection of 500 μg/500 μL TSLP antibody, 50 μL each time) groups. ELISA was applied to measure the serum levels of immunoglobulin E (IgE), ovalbumin (OVA)-sIgE, interleukin-4 (IL-4), IL-5, IL-13, and interferon-γ (IFN-γ); flow cytometry was employed to detect Treg cells and dendritic cell (DC) and lymphopoiesis. RT-qPCR and Western blot assays were used to measure the levels of TSLP, OX40L, T-bet, GATA-3, NF-κB, p38, and ERK. Treatment with LY294002 and anti-TSLP resulted in increases in the numbers of total cells, eosinophils, neutrophils, and lymphocytes in the bronchoalveolar lavage fluid; total serum levels of IgE, OVA-sIgE, IL-4, IL-5, and IL-13; levels of DC cells; lymphopoiesis; and levels of TSLP, OX40L, GATA-3, NF-κB, p38, and ERK, whereas there were decreases in the levels of IFN-γ and CD4CD25Treg cells; CD4Foxp3Treg cells; and T-bet. The TSLP-DC-OX40L pathway may contribute to asthma pathogenesis and airway inflammation by modulating the levels of CD4CD25Treg cells and inflammatory cytokines.