PAR acclimation and UVBR-induced DNA damage in Antarctic marine microalgae

Whether or not it is related to stratospheric ozone depletion, Antarctic microalgae experience ultraviolet-B radiation (UVBR) stress in situ, leading to decreased photosynthetic performance, DNA damage, and/or altered community composition. UVBR vulnerability is known to be species specific, but may also be affected by a range of environmental growth conditions, including the light history of the cells. This study investigates the influence of acclimation to photosynthetically active radiation (PAR) on the vulnerability to UVBR-induced DNA damage in Antarctic microalgae. Chaetoceros dichaeta, Pyramimonas gelidicola, Phaeocystis antarctica and Polarella glacialis were acclimated to 5 PAR levels, after which growth rate, pigment composition, malondialdehyde (MDA, a general indicator of oxidative stress) and UV-absorbing compounds were measured. Photoacclimated cultures were then exposed to a single UVBR treatment and the accumulation of UVBR-induced DNA damage was determined by the number of cyclobutane pyrimidine dimers (CPDs). Acclimation to increasing irradiance enhanced both the xanthophyll to chlorophyll a ratio and xanthophyll deepoxidation in all species. Increased cellular MDA levels were found at the highest irradiance in all species except P. gelidicola. Yet, growth rates were only reduced at the 2 lowest PAR levels. P. antarctica and P. glacialis showed a strong linear induction of UV-absorbing compounds at increasing PAR intensities, whereas P. gelidicola showed no induction of these compounds. The UVBR treatment induced CPDs in P. gelidicola only, and CPD levels were elevated at the highest PAR acclimation intensities. Thus, sensitivity to UVB-induced CPD accumulation was species specific, and, counterintuitively, acclimation to high PAR increased the sensitivity of P. gelidicola to UVB-induced DNA damage

Becker muscular dystrophy patients with deletions around exon 51; a promising outlook for exon skipping therapy in Duchenne patients.

Item does not contain fulltextTheoretically, 13% of patients with Duchenne muscular dystrophy may benefit from antisense-mediated skipping of exon 51 to restore the reading frame, which results in the production of a shortened dystrophin protein. We give a detailed description with longitudinal follow up of three patients with Becker muscular dystrophy with in-frame deletions in the DMD gene encompassing exon 51. Their internally deleted, but essentially functional, dystrophins are identical to those that are expected as end products in DMD patients treated with the exon 51 skipping therapy. The mild phenotype encourages further development of exon 51 skipping therapy.1 april 201

Propionic acidemia as a cause of adult-onset dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is extremely heterogeneous with a large proportion due to dominantly inherited disease-causing variants in sarcomeric genes. Recessive metabolic diseases may cause DCM, usually with onset in childhood, and in the context of systemic disease. Whether metabolic defects can also cause adult-onset DCM is currently unknown. Therefore, we performed an extensive metabolic screening in 36 consecutive adult-onset DCM patients. Diagnoses were confirmed by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Measurement of propionyl-CoA carboxylase (PCC) activity was done in fibroblasts. Whole exome sequencing (WES) data of 157 additional DCM patients were analyzed for genetic defects. We found a metabolic profile characteristic for propionic acidemia in a patient with severe DCM from 55 years of age. Genetic analysis demonstrated compound heterozygous variants in PCCA. Enzymatic activity of PCC in fibroblasts was markedly reduced. A targeted analysis of the PCCA and PCCB genes using available WES data from 157 further DCM patients subsequently identified another patient with propionic acidemia. This patient had compound heterozygous variants in PCCB, and developed severe DCM from 42 years of age. Adult-onset DCM can be caused by propionic acidemia, an autosomal recessive inheritable metabolic disorder usually presenting as neonatal or childhood disease. Current guidelines advise a low-protein diet to ameliorate or prevent detrimental aspects of the disease. Long-term follow-up of a larger group of patients may show whether this diet would also ameliorate DCM. Our results suggest that diagnostic metabolic screening to identify propionic acidemia and related disorders in DCM patients is justified

A Mutation Update for the FLNC Gene in Myopathies and Cardiomyopathies

Contains fulltext : 220374.pdf (Publisher’s version ) (Open Access

Update on Kleefstra syndrome

Kleefstra syndrome is characterized by the core phenotype of developmental delay/intellectual disability, (childhood) hypotonia and distinct facial features. The syndrome can be either caused by a microdeletion in chromosomal region 9q34.3 or by a mutation in the euchromatin histone methyltransferase 1 (EHMT1) gene. Since the early 1990s, 85 patients have been described, of which the majority had a 9q34.3 microdeletion (>85%). So far, no clear genotype-phenotype correlation could be observed by studying the clinical and molecular features of both 9q34.3 microdeletion patients and patients with an intragenic EHMT1 mutation. Thus, to further expand the genotypic and phenotypic knowledge about the syndrome, we here report 29 newly diagnosed patients, including 16 patients with a 9q34.3 microdeletion and 13 patients with an EHMT1 mutation, and review previous literature. The present findings are comparable to previous reports. In addition to our former findings and recommendations, we suggest cardiac screening during follow-up, because of the possible occurrence of cardiac arrhythmias. In addition, clinicians and caretakers should be aware of the regressive behavioral phenotype that might develop at adolescent/adult age and seems to have no clear neurological substrate, but is rather a so far unexplained neuropsychiatric featur