A novel desmin mutation leading to autosomal recessive limb-girdle muscular dystrophy: distinct histopathological outcomes compared with desminopathies.

BACKGROUND: Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a heterogeneous group of myopathies characterised by progressive muscle weakness involving proximal muscles of the shoulder and pelvic girdles including at least 17 different genetic entities. Additional loci have yet to be identified as there are families which are unlinked to any of the known loci. Here we have investigated a consanguineous family with LGMD2 with two affected individuals in order to identify the causative gene defect. METHODS AND RESULTS: We performed genome wide homozygosity mapping and mapped the LGMD2 phenotype to chromosome 2q35-q36.3. DNA sequence analysis of the highly relevant candidate gene DES revealed a homozygous splice site mutation c.1289-2A>G in the two affected family members. Immunofluorescent staining and western blot analysis showed that the expression and the cytoskeletal network formation of mutant desmin were well preserved in skeletal muscle fibres. Unlike autosomal dominant desminopathies, ultrastructural alterations such as disruption of myofibrillar organisation, formation of myofibrillar degradation products and dislocation/aggregation of membranous organelles were not present. This novel splice site mutation results in addition of 16 amino acids within the tail domain of desmin, which has been suggested to interact with lamin B protein. We also detected a specific disruption of desmin-lamin B interaction in the skeletal muscle of the patient by confocal laser scanning microscopy. CONCLUSIONS: Our study reveals that autosomal recessive mutations in DES cause LGMD2 phenotype without features of myofibrillar myopathy.

HHV-6 is ubiquitously found using Western blot in tonsils and adenoid tissues of healthy people.

Few studies have examined the prevalence and cellular proclivity of latent human herpesvirus 6 (HHV-6) in healthy populations. Difficulties in detection of HHV-6 genome in different tissues using polymerase chain reaction (PCR) and immunohistochemistry (IHC) techniques have been reported by various researchers. We examined tonsils and adenoid tissues of 54 patients who had undergone tonsillectomy or adenoidectomy without any evidence of acute infection for the presence of latent HHV-6 infection. While we were investigating the prevalence of HHV-6, we tested the efficiency of PCR, IHC and Western Blot (WB) for detection of HHV-6 in tonsil tissues. We found that 100% of tonsil tissues were positive for HHV-6 with WB, 40% of tonsils were positive with PCR and no tonsil was positive with IHC. This result correlates well with most studies claiming HHV-6 is a ubiquitous organism in various populations and tissues. Western blot may be a good choice for detecting HHV-6 in tissues. Expression of the HHV-6 gp60/110 envelope protein disclosed by WB may indicate that HHV-6 does not have true latency. To our knowledge, this is the first report to use WB to test for HHV-6 in tissues.

Long non-coding RNAs in the atherosclerotic plaque.

BACKGROUND AND AIMS: Genetic and environmental factors are important components of the development of atherosclerosis. Long non-coding RNA (lncRNAs) have emerged as regulators of multiple pathophysiological pathways in the cardiovascular system. Here, we investigated potential associations between lncRNAs and atherosclerosis. METHODS: Tissue samples from atherosclerotic coronary artery plaques and non-atherosclerotic internal mammary artery were obtained from 20 patients during coronary artery bypass surgery. Expression levels of five lncRNAs known to be associated with coronary artery disease were measured using quantitative PCR. RESULTS: Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL) and myocardial infarction-associated transcript (MIAT) were more expressed in the atherosclerotic arteries compared to the non-atherosclerotic arteries. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was less expressed in the atherosclerotic plaques. Expression levels of potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) and hypoxia inducible factor 1A antisense RNA 2 (aHIF) were comparable between atherosclerotic and non-atherosclerotic arteries. In the atherosclerotic plaque, expression levels of MALAT1, MIAT, KCNQ1OT1 and aHIF were inversely correlated with age. CONCLUSIONS: We report significant associations between lncRNAs and atherosclerosis. These findings support a role for lncRNAs in coronary artery disease development.