Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: Results of the TRIDENT study

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin

Expression of Ano6 in C2C12 muscle cells and mouse skeletal muscle.

<p>(A) Semi-quantitative RT-PCR analysis of Ano6 and GAPDH expression in C2C12 cells during differentiation. (B) Relative expression of Ano6 (normalized to GAPDH) examined by qRT-PCR in C2C12 cells during differentiation. (C) Relative expression of Ano6 (normalized to GAPDH) examined by qRT-PCR in the quadriceps muscles of mice at 6 days, 6 weeks and 6 months of age. **p<0.01; ***p<0.001.</p

Neurodevelopmental and other phenotypes recurrently associated with heterozygous BAZ2B loss-of-function variants

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 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