Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

Peer reviewe

Role of cytoskeletal abnormalities in the neuropathology and pathophysiology of type I lissencephaly

Type I lissencephaly or agyria-pachygyria is a rare developmental disorder which results from a defect of neuronal migration. It is characterized by the absence of gyri and a thickening of the cerebral cortex and can be associated with other brain and visceral anomalies. Since the discovery of the first genetic cause (deletion of chromosome 17p13.3), six additional genes have been found to be responsible for agyria–pachygyria. In this review, we summarize the current knowledge concerning these genetic disorders including clinical, neuropathological and molecular results. Genetic alterations of LIS1, DCX, ARX, TUBA1A, VLDLR, RELN and more recently WDR62 genes cause migrational abnormalities along with more complex and subtle anomalies affecting cell proliferation and differentiation, i.e., neurite outgrowth, axonal pathfinding, axonal transport, connectivity and even myelination. The number and heterogeneity of clinical, neuropathological and radiological defects suggest that type I lissencephaly now includes several forms of cerebral malformations. In vitro experiments and mutant animal studies, along with neuropathological abnormalities in humans are of invaluable interest for the understanding of pathophysiological mechanisms, highlighting the central role of cytoskeletal dynamics required for a proper achievement of cell proliferation, neuronal migration and differentiation

Imaging Physicochemical Reactions Occurring at the Pore Surface in Binary Bioactive Glass Foams by Micro Ion Beam Analysis

In this work, the physicochemical reactions occurring at the surface of bioactive sol−gel derived 3D glass scaffolds via a complete PIXE characterization were studied. 3D glass foams in the SiO2−CaO system were prepared by sol−gel route. Samples of glass scaffolds were soaked in biological fluids for periods up to 2 days. The surface changes were characterized using particle induced X-ray emission (PIXE) associated to Rutherford backscattering spectroscopy (RBS), which are efficient methods to perform quantitative chemical maps. Elemental maps of major and trace elements at the glass/biological fluids interface were obtained at the micrometer scale for every interaction time. Results revealed interconnected macropores and physicochemical reactions occurring at the surface of pores. The micro-PIXE-RBS characterization of the pores/biological fluids interface shows the glass dissolution and the rapid formation of a Ca rich layer with the presence of phosphorus that came from biological fluids. After 2 days, a calcium phosphate-rich layer containing magnesium is formed at the surface of the glass scaffolds. We demonstrate that quantities of phosphorus provided only by the biological medium have a significant impact on the development and the formation of the phosphocalcic layer

[Management of muscle and nerve biopsies: expert guidelines from two French professional societies, Société française de myologie et de l'Association française contre les myopathies] : Prise en charge des biopsies musculaires et nerveuses. Recommandations formalisées d'experts sous l'égide de la Société française de neuropathologie, de la Société française de myologie et de l'Association française contre les myopathies

International audienc

Variants in CLDN5 cause a syndrome characterized by seizures, microcephaly and brain calcifications

The blood brain barrier ensures central nervous system homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the BBB. We have identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype-phenotype correlations. We modeled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients likely result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

Variants in CLDN5 cause a syndrome characterized by seizures, microcephaly and brain calcifications.

The blood brain barrier ensures central nervous system homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the BBB. We have identified de novo heterozygous missense variants in CLDN5 in fifteen unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype-phenotype correlations. We modeled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients likely result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood brain barrier and impaired neuronal function