Project description:The objective of this study is to resequence of targeted intervals containing autosomal recessive variants causing neurological disorders in consanguineous pedigrees. Using homozygosity mapping, three intervals of very different sizes have previously been unambiguously mapped for three different neurological diseases: 2.4Mb, 8Mb and 14.3Mb in size, for Microlissencephaly, Severe Mental Retardation and Complicated hereditary spastic paraplegia respectively. This study is a pilot to assess how well custom targeted resequencing performs across a broad size range of intervals. The study design is to use a different custom capture probe set for each interval, pulldown from a single patient from each family, and sequence 1 lane using Illumina paired-reads for each sample. Candidate variants will be followed up in the families themselves, and in patients with similar phenotypes from outbred populations.
Project description:26 limb-girdle muscular dystrophy patients from Latvia and 34 patients from Lithuania with clinical symptoms of limb-girdle muscular dystrophies, along with 204 healthy unrelated controls were genotyped for 96 most frequent known limb-girdle muscular dystrophies causing mutations for the region, using VeraCode GoldenGate system. More information can be found in article Robust genotyping tool for autosomal recessive type of limb-girdle muscular dystrophies in BMC Musculoskeletal Disorders by I. Inashkina et al.
Project description:Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease characterized by autosomal recessive mutations in the sacsin gene (SACS), that cause in patients progressive cerebellar atrophy, damage of the peripheral nerves, and significant retinal changes and cognitive impairment. No effective therapies have been proposed for ARSACS, even if some evidences suggest that powerful antioxidant agents can be considered a therapeutic tool. Resveratrol (Res) is a natural polyphenol compound derived from vegetal sources, the application of which in biomedicine is increasing in the latest years because of its significant therapeutic effects, in particular in neurodegenerative diseases. In this study, we provide evidences about its potential exploitation in the treatment of ARSACS. Because of the low solubility of resveratrol in physiological media, a nanoplatform based on nanostructured lipid carriers is here proposed for its encapsulation and delivery. Resveratrol-loaded nanostructured lipid carriers (Res-NLCs) have been synthetized, characterized, and tested on healthy and ARSACS patient fibroblasts. Nanovectors displayed optimal stability and biocompatibility, and excellent antioxidant and anti-inflammatory activities. A comprehensive investigation at gene (with real-time quantitative RT-PCR (qRT-PCR)) and protein (with proteomics) level demonstrated the therapeutic potential of Res-NLCs, encouraging future investigations on pre-clinical models.