Expanding the Clinical and Molecular Spectrum of FOXG1- and ZBTB18-Associated Neurodevelopmental Disorders.

Introduction: The zinc finger BTB domain-containing protein ZBTB18 binds to FOXG1 to form a transcriptional repressive complex involved in neuronal differentiation. Disruption of the components of this complex results in chromosome 1q43-q44 deletion syndrome/intellectual developmental disorder 22 or in FOXG1 syndrome.

Case Presentation: This study reports on five patients with cognitive and behavioral impairment, seizures, microcephaly, and/or congenital brain abnormalities.

Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability.

Intellectual disability (ID), a neurodevelopmental disorder affecting 1-3% of the general population, is characterized by limitations in both intellectual function and adaptive skills. The high number of conditions associated with ID underlines its heterogeneous origin and reveals the difficulty of obtaining a rapid and accurate genetic diagnosis. However, the Next Generation Sequencing, and the whole exome sequencing (WES) in particular, has boosted the diagnosis rate associated with ID.

From neural stem cells to glioblastoma: A natural history of GBM recapitulated in vitro.

Due to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that have complicated the development of effective therapeutic strategies.

Expanding the clinical and molecular spectrum of the CWC27-related spliceosomopathy.

Cyclophilins are a type of peptidyl-prolyl cis-trans isomerases. CWC27, one of the known human cyclophilins, is recruited by the spliceosome for the pre-mRNA splicing process. Biallelic deleterious variants in CWC27 lead to a spectrum of overlapping phenotypes including retinal degeneration, skeletal anomalies, short stature, and neurological defects.

PLGA:poloxamer and PLGA:poloxamine blend nanoparticles: new carriers for gene delivery.

The main objective of the present work was the development of new nanoparticulate carrier systems for the delivery of plasmid DNA. These new carriers consist of a blend matrix formed by a poly(lactic-co-glycolic acid) (PLGA) copolymer and polyoxyethylene derivatives. More specifically, we have prepared nanostructures with different PLGA:poloxamer and PLGA:poloxamine compositions by an optimized emulsification-solvent diffusion technique and studied the potential of these carriers for the encapsulation and controlled release of plasmid DNA.

Inhibition of Cdk4 activity enhances translation of p27kip1 in quiescent Rb-negative cells.

We show in this work that the inhibition of Cdk4 (6) in Rb(-/-) 3T3 cells enhances the accumulation of the p27(kip1) cyclin-dependent kinase inhibitor when these cells are induced into quiescence. Two different forms of inhibition of Cdk4 (6), namely overexpression of the Cdk4 (6) inhibitor p16 and overexpression of a dominant negative mutant of Cdk4 (Cdk4(N158)), result in this effect. This suggests that the relevant activity of Cdk4 (6) that has to be inactivated in this setting is its kinase activity.