13 research outputs found
Effect of Morphology and Dispersibility of Silica Nanoparticles on the Mechanical Behaviour of Cement Mortar
Improvement compressive strength of cementitious composites in different curing media by incorporating ZrO2 nanoparticles
Grouts for Injection of Historical Masonries: Influence of the Binding System and Other Additions on the Properties of the Matrix
Use of colloidal silica to obtain a new inert from municipal solid waste incinerator (MSWI) fly ash: first results about reuse
Exome sequencing reveals a nebulin nonsense mutation in a dog model of nemaline myopathy
Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches