ABSTRACT
Leber congenital amaurosis (LCA) encompasses a group of severe inherited retinal dystrophies (IRDs) responsible for early childhood blindness. There are currently 25 genes implicated in the pathogenesis of these diseases, and identification of disease-causing variants will be required for personalised therapies. Whole exome and whole genome sequencing is informative for detecting novel disease-causing genes, whilst next-generation sequencing has excelled at detecting novel variants in known disease-causing genes.A global effort will be required to identify patient populations for early intervention. At the Australian Inherited Retinal Disease Registry and DNA Bank, we seek to identify genetic variants in individuals with IRDs in the Australian population to identify potential candidates for clinical trials, to inform clinical management of patients including reproductive options and to expand existing knowledge of IRDs.Due to the diversity of genes implicated, personalised strategies are likely to be the benchmark for treating these diseases, and a combined approach of different therapies may be optimal in treating some of these diseases.
Subject(s)
Leber Congenital Amaurosis/genetics , Precision Medicine , Acyltransferases/genetics , Antigens, Neoplasm/genetics , Australia/epidemiology , Cell Cycle Proteins , Cytoskeletal Proteins , DNA Mutational Analysis , Genetic Heterogeneity , Genetic Therapy , Genetic Vectors/therapeutic use , High-Throughput Nucleotide Sequencing , Humans , Leber Congenital Amaurosis/epidemiology , Leber Congenital Amaurosis/therapy , Molecular Targeted Therapy , Neoplasm Proteins/genetics , Registries , Exome Sequencing , Whole Genome Sequencing , cis-trans-Isomerases/geneticsABSTRACT
Pax3 and Pax7 are powerful myogenic inducers and hence play a critical role in skeletal muscle development and regeneration. In this paper we discuss the role of Pax3 and Pax7 in dorsal patterning of the somite with subsequent determination of myogenic precursor cells for muscle formation within the developing embryo and in adult muscle. Recent evidence of the ability of stem cells to contribute to muscle regeneration in adult tissues, and the role of Pax7 in conversion of multipotent stem cells to the myogenic lineage are also discussed. Several tissue specific Pax7 transcripts that encode isoforms with different DNA binding characteristics and potentially distinct transactivation specificities are identified. The expression of a range of transcripts in the determination of different tissue lineages and distinct cell populations both in the embryo and in the adult indicates an extraordinary level of complexity. A detailed understanding of these molecules and their functions during embryogenesis and adult muscle formation is imperative for future stem cell therapies.
