ITPR3-associated neuropathy: Report of a further family with adult onset intermediate Charcot-Marie-Tooth disease.

Background And Purpose: ITPR3 encodes type 3 inositol-tri-phosphate receptor (IPR3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot-Marie-Tooth disease (CMT).

Methods: We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years.

Insights into phenotypic variability caused by GARS1 pathogenic variants.

Background And Purpose: Pathogenic variants of the glycyl-tRNA synthetase 1 (GARS1) gene have been described as a cause of Charcot-Marie-Tooth disease type 2D, motor axonal neuropathy with upper limb predominance (distal hereditary motor neuropathy [dHMN] type V), and infantile spinal muscular atrophy.

Methods: This cross-sectional, retrospective, observational study was carried out on 12 patients harboring the c.794C>T (p.

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion.

Objective: Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset.

Methods: This cross-sectional, multicenter cohort study applied clinical and functional evaluation.

A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy.

Aims: We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes.

Methods: We performed whole-exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected.

Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene.

IMMT gene codes for mitofilin, a mitochondrial inner membrane protein that regulates the morphology of mitochondrial cristae. The phenotype associated with mutations in this gene has not been yet established, but functional studies carried out show that its loss causes a mitochondrial alteration, both in the morphology of the mitochondrial crests and in their function. We present two cousins from an extended highly consanguineous family with developmental encephalopathy, hypotonia, nystagmus due to optic neuropathy.

A study of the phenotypic variability and disease progression in Laing myopathy through the evaluation of muscle imaging.

Background: Laing myopathy is characterized by broad clinical and pathological variability. They are limited in number and protocol of study. We aimed to delineate muscle imaging profiles and validate imaging analysis as an outcome measure.

Cardiac protein changes in ischaemic and dilated cardiomyopathy: a proteomic study of human left ventricular tissue.

The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM).

Differences in MEF2 and NFAT transcriptional pathways according to human heart failure aetiology.

Background: Ca(2+) handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue.

Methodology And Principal Findings: A total of 83 hearts from ischemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (CNT, n = 9) were analyzed by western blotting.

Influence of heart failure on nucleolar organization and protein expression in human hearts.

We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.

Influence of heart failure on nucleocytoplasmic transport in human cardiomyocytes.

Aims: The role of the cell nucleus in the development of heart failure (HF) is unknown, so the objectives of this study were to analyse the effect of HF on nucleocytoplasmic transport and density of the nuclear pore complex (NPC).

Methods And Results: A total of 51 human heart samples from ischaemic (ICM, n = 30) and dilated (DCM, n = 16) patients undergoing heart transplantation and control donors (CNT, n = 5) were analysed by western blotting. Subcellular distribution of proteins and NPC were analysed by fluorescence and electron microscopy, respectively.

Prenatal ethanol exposure alters the cytoskeleton and induces glycoprotein microheterogeneity in rat newborn hepatocytes.

Aims: Prenatal ethanol exposure (PEA) increases both liver weight and total protein content in the Golgi complex and alters its morphological and functional properties. As PEA-induced protein retention could be the synergetic consequence of alterations in the cytoskeleton and in the glycan biosynthesis, and there are no data that in liver PEA perturbs the cytoskeleton, we examined in hepatocytes whether PEA affects the main cytoskeleton elements. We also analysed whether ethanol induces glycoprotein microheterogeneity by altering the sugar composition of glycoproteins.

Chronic ethanol consumption enhances interleukin-1-mediated signal transduction in rat liver and in cultured hepatocytes.

Background: Interleukin-1 (IL-1) is a central mediator of the inflammatory process. Increased serum levels of IL-1 have been reported in alcoholics with liver damage, but it remains unknown whether chronic ethanol intake, in the presence or absence of lipopolysaccharide (LPS), activates IL-1 release and signaling in the hepatocyte.

Methods: IL-1beta and IL-10 release, expression of their receptors (IL-1RI and IL-10R), and the IL-1RI signal transduction response were evaluated in livers and cultured hepatocytes from ethanol-fed or pair-fed rats exposed in vivo or in vitro to LPS, ethanol, or both.