Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter.

Background: the protein phosphatase 3 catalytic subunit alpha (PPP3CA) gene encodes for the alpha isoform of the calcineurin catalytic subunit, which controls the phosphorylation status of many targets. Currently, 23 pathogenic variants of PPP3CA are known, with clinical manifestations varying by mutation type and domain.

Results: through whole exome sequencing, we found two de novo variants in PPP3CA: a frameshift variant predicted leading to a truncated protein in Pt.

Looks Can Be Deceiving: Diagnostic Power of Exome Sequencing in Debunking 15q11.2 Copy Number Variations.

: The pathogenetic role of 15q11.2 Copy Number Variations (CNVs) remains contentious in the scientific community, as microdeletions and microduplications in this region are linked to neurodevelopmental disorders with variable expressivity. This study aims to explore the diagnostic utility of Exome Sequencing (ES) in a cohort of pediatric patients with 15q11.

Fluorescent Water-Soluble Polycationic Chitosan Polymers as Markers for Biological 3D Imaging.

Over the last decades, various tissue-clearing techniques have broken the ground for the optical imaging of whole organs and whole-organisms, providing complete representative data sets of three-dimensional biological structures. Along with advancements in this field, the development of fluorescent markers for staining vessels and capillaries has offered insights into the complexity of vascular networks and their impact on disease progression. Here we describe the use of a modified water-soluble chitosan linked to cyanine dyes in combination with ethyl cinnamate-based optical tissue clearing for the 3D visualization of tissue vasculature in depth.

The burst of satellite DNA in Leptidea wood white butterflies and their putative role in karyotype evolution.

Satellite DNAs (satDNAs) are abundant components of eukaryotic genomes, playing pivotal roles in chromosomal organization, genome stability, and evolution. Here, we combined cytogenetic and genomic methods to characterize the satDNAs in the genomes of Leptidea butterflies. Leptidea is characterized by the presence of a high heterochromatin content, large genomes, and extensive chromosomal reshuffling as well as the occurrence of cryptic species.

Differential amplification and contraction of satellite DNAs in the distinct lineages of the beetle Euchroma gigantea.

Satellite DNA (satDNA) consists of tandem repeat sequences that typically evolve rapidly through evolutionary mechanisms, including unequal crossover, transposition events, and others. The evolutionary history of Euchroma gigantea is marked by complex chromosomal evolution between lineages, making this species an interesting model for understanding satDNA evolution at intraspecies level. Therefore, our aim was to comprehend the potential contribution of satDNAs to the greater chromosomal differentiation of evolutionary lineages in E.

Chromosomal and genomic analysis suggests single origin and high molecular differentiation of the B chromosome of .

Supernumerary chromosomes (B chromosomes) have been an intriguing subject of study. Our understanding of the molecular differentiation of B chromosomes from an interpopulation perspective remains limited, with most analyses involving chromosome banding and mapping of a few sequences. To gain insights into the molecular composition, origin, and evolution of B chromosomes, we conducted cytogenetic and next-generation sequencing analysis of the repeatome in the grasshopper across various populations.

Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions.

The human retina is a complex anatomical structure that has no regenerative capacity. The pathogenesis of most retinopathies can be attributed to inflammation, with the activation of the inflammasome protein platform, and to the impact of oxidative stress on the regulation of apoptosis and autophagy/mitophagy in retinal cells. In recent years, new therapeutic approaches to treat retinopathies have been investigated.

Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis-like syndrome.

Loss-of-function CHD2 (chromodomain helicase DNA-binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families.

Multimodal Intraoperative Neurophysiological Monitoring in Intramedullary Spinal Cord Tumors: A 10-Year Single Center Experience.

Objective: The study aimed at evaluating the efficacy and the ability of D-wave monitoring combined with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) to predict functional outcomes in intramedullary spinal cord tumor (IMSCT) surgery.

Methods: Between December 2011 and December 2020, all patients harboring IMSCT who underwent surgery at our institution were prospectively collected in a surgical spinal registry and retrospectively analyzed. Patient charts and surgical and histological reports were analyzed.

Defining the Learning Curve of the Exoscope in Spine Surgery.

Introduction: In recent years, introduction of the exoscope system has been responsible for a new era of optics in surgery. Such a system has started to be widely used in neurosurgery. More recently, the exoscope has also been increasingly used for spinal procedures.

Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study.

Background: The recent guidelines suggest the use of genome-wide analyses, such as whole exome sequencing (WES), at the beginning of the diagnostic approach for cases with suspected genetic conditions. However, in many realities it still provides for the execution of a multi-step pathway, thus requiring several genetic tests to end the so-called 'diagnostic odyssey'.

Methods: We reported the results of GENE Project (Genomic analysis Evaluation NEtwork): a multicentre prospective cohort study on 125 paediatric outpatients with a suspected genetic disease in which we performed first-tier trio-WES, including exome-based copy number variation analysis, in parallel to a 'traditional approach' of two/three sequential genetic tests.

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally.

CATSHL syndrome, a new family and phenotypic expansion.

We report the case of a 12-year-old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile-onset hearing loss. The CATSHL (CAmptodactyly - Tall stature - Scoliosis - Hearing Loss syndrome) syndrome was suspected, and molecular analysis revealed a hitherto unreported, monoallelic variant c.1861C>T (p.

Role of Enhanced Recovery after Surgery (ERAS) Protocol in the Management of Elderly Patients with Glioblastoma.

Objective: Among the already difficult management of neuro-oncological patients, the elderly population remains vulnerable. Because of the pathology and the comorbidities, they present a significantly higher rate of medical issues related to surgical management. Despite this, the surgical option, if feasible, remains the gold standard in these patients, and an Enhanced Recovery After Surgery (ERAS) protocol could improve the postoperative safety of the patients.

Growth and rupture of an intracranial aneurysm: the role of wall aneurysmal enhancement and CD68.

Introduction: Intracranial aneurysms occur in 3%-5% of the general population. While the precise biological mechanisms underlying the formation, growth, and sudden rupture of intracranial aneurysms remain partially unknown, recent research has shed light on the potential role of inflammation in aneurysm development and rupture. In addition, there are ongoing investigations exploring the feasibility of employing new drug therapies for controlling the risk factors associated with aneurysms.

A randomized prospective comparative study on sinonasal morbidity and quality of life of transsphenoidal endoscopic surgery for pituitary adenomas: endonasal versus trans-septal approach.

Purpose: Endoscopic endonasal transsphenoidal approach (Endonasal approach) is commonly used to treat pituitary adenomas. The extent of dissection possibly changes the anatomy and the physiology of the nasal cavities and could give rise to post-operative morbidity and the quality of life (QoL). The purpose of this study was to investigate sinonasal morbidity and general QoL in patients who underwent surgery for treatment of pituitary adenoma, comparing Endonasal and endoscopic trans-septal transsphenoidal approach (Trans-septal approach).