Search

Abstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. Results We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. Conclusions With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.

Abstract Background The vision loss in Leber hereditary optic neuropathy patients is due to mitochondrial DNA mutations. No treatment has shown a clear-cut benefit on a clinically meaningful end-point. However, clinical evidences suggest two therapeutic approaches: the reduction of the mutation load in heteroplasmic patients or the elevation of mitochondrial DNA amount in homoplasmic patients. Results Here we show that ketogenic treatment, in cybrid cell lines, reduces the percentage of the m.13094 T > C heteroplasmic mutation and also increases the mitochondrial DNA levels of the m.11778G > A mitochondrial genotype. Conclusions These results suggest that ketogenic diet could be a therapeutic strategy for Leber hereditary optic neuropathy.

The Moroccan coast is characterized by a diversity of climate, reflecting a great richness and diversity of fauna and flora. By this, marine microbiota plays a fundamental role in many biogeochemical processes, environmental modifications, and responses to temperature changes. To date, no exploration by high-throughput techniques has been carried out on the characterization of the Moroccan marine microbiota. The objective of this work is to study the diversity and metabolic functions of MMM from the Moroccan coast (Atlantic and Mediterranean) according to the water source (WS) and the type of climate (CT) using the approach high-throughput sequencing of the 16SrRNA gene. Four water samples of twelve sampling sites from the four major climates along the Moroccan coastline were collected, and prokaryotic DNA was extracted. V4 region of 16S rRNA gene was amplified, and the product PCR was sequenced by Illumina Miseq. The β-diversity and α-diversity indices were determined to assess the species richness and evenness. The obtained results were analyzed by Mothur and R software. A total of twenty-eight Bacterial phyla and twelve Archaea were identified from the samples. Proteobacteria, Bacteroidetes, and Cyanobacteria are the three key bacterial phyla, and the Archaeal phyla identified are: Euryarchaeota, Nanoarchaeaeota, Crenarchaeota, Hydrothermarchaeota, Asgardaeota, Diapherotrites, and Thaumarchaeota in the Moroccan coastline and the four climates studied. The whole phylum are involved in marine biogeochemical cycles, and through their functions they participate in the homeostasis of the ocean in the presence of pollutants or stressful biotic and abiotic factors. In conclusion, the obtained results reported sufficient deepness of sequencing to cover the majority of Archaeal and Bacterial genera in each site. We noticed a strong difference in microbiota diversity, abundance, and taxonomy inter- and intra-climates and water source without significant differences in function. To better explore this diversity, other omic approaches can be applied such as the metagenomic shotgun, and transcriptomic approaches allowing a better characterization of the Moroccan marine microbiota and to understand the mechanisms of its adaptation and its impacts in/on the ecosystem.

Mitochondria are the cell’s power site, transforming energy into a form that the cell can employ for necessary metabolic reactions. These organelles present their own DNA. Although it codes for a small number of genes, mutations in mtDNA are common. Molecular genetics diagnosis allows the analysis of DNA in several areas such as infectiology, oncology, human genetics and personalized medicine. Knowing that the mitochondrial DNA is subject to several mutations which have a direct impact on the metabolism of the mitochondrion leading to many diseases, it is therefore necessary to detect these mutations in the patients involved. To date numerous mitochondrial mutations have been described in humans, permitting confirmation of clinical diagnosis, in addition to a better management of the patients. Therefore, different techniques are employed to study the presence or absence of mitochondrial mutations. However, new mutations are discovered, and to determine if they are the cause of disease, different functional mitochondrial studies are undertaken using transmitochondrial cybrid cells that are constructed by fusion of platelets of the patient that presents the mutation, with rho osteosarcoma cell line. Moreover, the contribution of next generation sequencing allows sequencing of the entire human genome within a single day and should be considered in the diagnosis of mitochondrial mutations.