The bromodomain adjacent to zinc finger 2B (BAZ2B) gene encodes a chromatin remodeling protein that has been shown to perform a variety of regulatory functions. It has been proposed that loss of... Show moreThe bromodomain adjacent to zinc finger 2B (BAZ2B) gene encodes a chromatin remodeling protein that has been shown to perform a variety of regulatory functions. It has been proposed that loss of BAZ2B function is associated with neurodevelopmental phenotypes, and some recurrent structural birth defects and dysmorphic features have been documented among individuals carrying heterozygous loss-of-function BAZ2B variants. However, additional evidence is needed to confirm that these phenotypes are attributable to BAZ2B deficiency. Here, we report 10 unrelated individuals with heterozygous deletions, stop-gain, frameshift, missense, splice junction, indel, and start-loss variants affecting BAZ2B. These included a paternal intragenic deletion and a maternal frameshift variant that were inherited from mildly affected or asymptomatic parents. The analysis of molecular and clinical data from this cohort, and that of individuals previously reported, suggests that BAZ2B haploinsufficiency causes an autosomal dominant neurodevelopmental syndrome that is incompletely penetrant. The phenotypes most commonly seen in association with loss of BAZ2B function include developmental delay, intellectual disability, autism spectrum disorder, speech delay-with some affected individuals being non-verbal-behavioral abnormalities, seizures, vision-related issues, congenital heart defects, poor fetal growth, and an indistinct pattern of dysmorphic features in which epicanthal folds and small ears are particularly common. Show less
Mycobacterium tuberculosis Resuscitation-promoting factor proteins (Rpf) induce stronger T-cell responses in latently infected individuals (LTBI) than in pulmonary tuberculosis patients (PTB), but... Show moreMycobacterium tuberculosis Resuscitation-promoting factor proteins (Rpf) induce stronger T-cell responses in latently infected individuals (LTBI) than in pulmonary tuberculosis patients (PTB), but there are scarce data concerning the responses to Rpf among LTBI with different contact levels. We therefore enrolled LTBI individuals infected through household contacts with PTB as well as people with community exposure who were determined to be LTBI through Interferon-γ (IFN-γ) release assays (IGRAs) and TB antibodies test, and we studied interferon-gamma responses to Rv0867c and Rv2389c which demonstrated the highest recognition of all Rpfs. The results demonstrated that LTBI infected through household contacts possessed higher interferon-gamma production and higher frequencies of CD4(+)IFN-γ(+) T-cells to Rv0867c and Rv2389c than did the community exposed individuals. These findings suggest that the interferon-gamma response to Rv0867c and Rv2389c may help to distinguish LTBI caused by different levels of exposure to M. tuberculosis. Show less