Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis

The aim of the present study was to report a novel mutation in the retinoschisin 1 (RS1) gene in a Caucasian family affected by X-linked juvenile retinoschisis (XLRS) and to describe the long-term modification of retinal structure. Two brothers with an early onset maculopathy were diagnosed with XLRS. Fundus photography, fluorescein angiography, spectral domain optical coherence tomography and electroretinogram analyses were performed. Their sister was also examined. All subjects were screened for mutations in the RS1 gene. XLRS patients demonstrated a marked reduction of best-corrected visual acuity. SD-OCT scans reported a cystic degeneration primarily involving the inner nuclear layer, though some cysts were detected in the outer plexiform layer and in the ganglion cell layer. During the ten-year follow-up, a progressive retinal thickening and coalescence of the cysts was observed. Genetic testing revealed a novel mutation (p.Ile212Asn) in the RS1 gene in both XLRS patients, whereas their sister was not a genetic carrier. Several mutations of the RS1 gene were recognized to be responsible for XLRS. Although the correspondence between genotype and phenotype is still under debate, is reasonable that siblings affected by XLRS could share other genetic and/or epigenetic factors capable to influence clinical course of the disease

Non\u2011syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3 like matrix AAA peptidase subunit 2 gene

Autosomal dominant optic atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. In an attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19-year-old male that had been affected by isolated DOA since childhood. The exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) gene, a gene known to be associated with spinocerebellar ataxia. The patient did not show any signs other than DOA. Thus, the result demonstrates the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal DOA

Fifty Hertz electromagnetic field exposure stimulates secretion of β-amyloid peptide in cultured human neuroglioma

Recent epidemiological studies raise the possibility that individuals with occupational exposure to low frequency (50-60 Hz) electromagnetic fields (LF-EMF), are at increased risk of Alzheimer's disease (AD). However, the mechanisms through which LF-EMF may affect AD pathology are unknown. We here tested the hypothesis that the exposure to LF-EMF may affect amyloidogenic processes. We examined the effect of exposure to 3.1 mT 50 Hz LF-EMF on Abeta secretion in H4 neuroglioma cells stably overexpressing human mutant amyloid precursor protein. We found that overnight exposure to LF-EMF induces a significant increase of amyloid-beta peptide (Abeta) secretion, including the isoform Abeta 1-42, without affecting cell survival. These findings show for the first time that exposure to LF-EMF stimulates Abeta secretion in vitro, thus alluding to a potential link between LF-EMF exposure and APP processing in the brain

Lymphocytes from Autoimmune MRL<i>lpr/lpr</i>Mice Are Hyperresponsive to IL-18 and Overexpress the IL-18 Receptor Accessory Chain

AbstractMRL lpr/lpr mice spontaneously develop a severe autoimmune lupus syndrome characterized by strong autoantibody production and massive lymphoproliferation, in which IFN-γ plays a major pathogenic effect. The role of the IFN-γ-inducing cytokine IL-18 in the autoimmune syndrome of lpr/lpr mice has been investigated. In response to IL-18, lymph node cells of lpr/lpr mice produce significant amounts of IFN-γ and proliferate more potently as compared with cells from +/+ mice. Cells likely responsible for such hyperresponsiveness to IL-18 include NK cells and the CD4+/CD8+ self-reactive T lymphocytes characteristically present in lymph nodes of lpr/lpr mice. Analysis of the expression of IL-18R complex revealed that mRNA for the IL-18Rα-chain is constitutively expressed at similar level both in +/+ and lpr/lpr lymphocytes. In contrast, the expression of the accessory receptor chain IL-18Rβ is low in unstimulated +/+ cells but significantly high in lpr/lpr cells. Thus, the abnormally high expression of the IL-18R chain IL-18Rβ could be one of the causes of the hyperresponsiveness of lpr/lpr cells to IL-18 at the basis of consequent enhancement of IFN-γ production and development of IFN-γ-dependent autoimmune pathology

A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review

Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y490N). These two rare missense mutations have previously been reported with other heterozygous mutations. However, their co-occurrence in a KD patient is novel. From the perspective of this case, we review the current literature on compound heterozygous mutations in adult-onset KD and their phenotypic variability

Octopamine, unlike other trace amines, inhibits responses of astroglia-enriched cultures to lipopolysaccharide via a β-adrenoreceptor-mediated mechanism

none7Trace amines (TAs), i.e. β-phenylethylamine, tyramine and octopamine, are generally regarded as sympathomimetic compounds with structural and functional analogy with catecholamines. Previous reports have shown particularly high levels of circulating TAs in migraine and cluster headache patients. However, no clues are yet available as to the pathophysiological significance of these alterations. The effect of different TAs on the release of nitric oxide was investigated in rat astroglial cells stimulated with lipopolysaccharide (LPS). Octopamine substantially inhibited the release of NO evoked by LPS. Tyramine and β-PEA were ineffective. The inhibitory effect of octopamine was fully reverted by two selective antagonists of β-adrenergic receptors, while α-adrenergic blockade was ineffective. These data, consistent with a role of octopamine as a modulator of NO release, uncover an interaction between octopamine and β-adrenergic receptors in astroglial cells. These results may have an impact in understanding the mechanisms underlying migraine pathophysiologymixedG. D'Andrea; A. D'Arrigo; F. Facchinetti; E. Del Giudice; D. Colavito; D. Bernardini; A. LeonG., D'Andrea; A., D'Arrigo; F., Facchinetti; E., Del Giudice; D., Colavito; Bernardini, Daniele; A., Leo

Non-syndromic isolated dominant optic atrophy caused by the p.R468C mutation in the AFG3L2 gene

Background: Autosomal Dominant Optic Atrophy (DOA) is the most frequent form of hereditary optic atrophy, a disease presenting with considerable inter- and intra-familial clinical variability. Although a number of mutations in different genes are now known to cause DOA, many cases remain undiagnosed. Methods: In attempt to identify the underlying genetic defect, whole exome sequencing was performed in a 19 years old male affected by isolated DOA since childhood. Results: Exome sequencing revealed a pathogenic mutation (p.R468C, c.1402C>T) in the AFG3L2 gene, a gene known to be associated with spinocerebellar ataxia. Our patient does not show any signs other than DOA. Conclusions: Our result raises the possibility that mutations in the AFG3L2 gene may be a cause of isolated autosomal dominant optic atrophy

Are CSNK2A1 gene mutations associated with retinal dystrophy? Report of a patient carrier of a novel de novo splice site mutation

Report of a patient carrier of a novel de novo splice site mutation in CSNK2A1 gene associated with retinal dystroph