Genetic Landscape of Non-Remitting Neutropenia in Children and Chronic Idiopathic Neutropenia in Adults.

Non-remitting neutropenia in children and chronic idiopathic neutropenia (CIN) in adults have been described previously as peculiar subgroups of neutropenic patients carrying similar clinical and immunological features. The present collection comprising 25 subjects (16 adults and 9 children) mostly affected with mild (84%) and moderate (16%) neutropenia aimed to identify the underlying (possibly common) genetic background. The phenotype of these patients resemble the one described previously: no severe infections, presence of rheumathological signs, leukopenia in almost all patients and lymphocytopenia in one-third of the cohort.

A multi-omics approach reveals impaired lipid metabolism and oxidative stress in a zebrafish model of Alexander disease.

Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in the GFAP gene. To date, several in vitro and in vivo models have been generated in an attempt to unravel the main mechanisms underlying this complex disease. However, none of these models is suitable for investigating the global dysregulation caused by AxD.

A systematic review and meta-analysis of GFAP gene variants in Alexander disease.

Alexander disease (ALXDRD) is a rare neurodegenerative disorder of astrocytes resulting from pathogenic variants in the GFAP gene. The genotype-phenotype correlation remains elusive due to the variable expressivity of clinical manifestations. In an attempt to clarify the effects of GFAP variants in ALXDRD, numerous studies were collected and analyzed.

Genotype-Phenotype Correlation and Functional Insights for Two Monoallelic Missense Variants Affecting the Catalytic Core.

The TREX1 exonuclease degrades DNA to prevent aberrant nucleic-acid sensing through the cGAS-STING pathway, and dominant Aicardi-Goutières Syndrome type 1 (AGS1) represents one of numerous -related autoimmune diseases. Monoallelic mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.

Beneficial Effect of Phenytoin and Carbamazepine on Gene Expression and Mutant GFAP Folding in a Cellular Model of Alexander's Disease.

Alexander's disease (AxD) is a rare, usually relentlessly progressive disorder of astroglial cells in the central nervous system related to mutations in the gene encoding the type III intermediate filament protein, glial fibrillary acidic protein (GFAP). The pathophysiology of AxD is only partially understood. Available data indicate that an excessive GFAP gene expression may play a role.

Flu and Pneumococcal Vaccine Coverage in Scleroderma Patients Still Need to Be Prompted: A Systematic Review.

Systemic sclerosis (scleroderma, SSc) is an autoimmune connective tissue disease characterized by excessive production of collagen and multiorgan involvement. Scleroderma patients are at increased risk of influenza complications and pneumonia; thus, vaccinations are recommended. This systematic review evaluated the influenza and pneumococcus vaccination coverage for SSc patients.

The Gene Is Involved in Hirschsprung Associated Enterocolitis Susceptibility through an Altered Downstream Signaling.

Hirschsprung (HSCR) Associated Enterocolitis (HAEC) is a common life-threatening complication in HSCR. HAEC is suggested to be due to a loss of gut homeostasis caused by impairment of immune system, barrier defense, and microbiome, likely related to genetic causes. No gene has been claimed to contribute to HAEC occurrence, yet.

Alexander Disease Modeling in Zebrafish: An In Vivo System Suitable to Perform Drug Screening.

Alexander disease (AxD) is a rare astrogliopathy caused by heterozygous mutations, either inherited or arising de novo, on the glial fibrillary acid protein (GFAP) gene (17q21). Mutations in the GFAP gene make the protein prone to forming aggregates which, together with heat-shock protein 27 (HSP27), αB-crystallin, ubiquitin, and proteasome, contribute to form Rosenthal fibers causing a toxic effect on the cell. Unfortunately, no pharmacological treatment is available yet, except for symptom reduction therapies, and patients undergo a progressive worsening of the disease.