Characterisation Of A Novel Human Neuromuscular Disease Associated With Deficiency Of The Syntrophins And Dystrobrevin.
Funder
National Health and Medical Research Council
Funding Amount
$284,069.00
Summary
The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affec ....The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affected babies are never able to breathe adequately, and die during the first weeks of life. No specific treatment is currently available. Until recently the underlying gene and protein abnormalities resulting in the majority of cases of muscular dystrophy were unknown and hence definitive diagnosis and prenatal diagnosis was not possible. We have recently identified deficiency of a group of muscle proteins, the syntrophins and dystrobrevin, in 15 children with severe weakness, in whom the cause was previously unknown. This group of patients represent the first examples of a novel neuromuscular disorder. We will now identify the disease-causing genetic mutations in these patients and determine how abnormalities in these muscle proteins lead to muscle weakness and degeneration. This research will have immediate application to clinical practice as we will be able to give the childrens' families accurate information about the risk to future offspring and offer prenatal diagnosis. In addition, it will provide new and important information concerning the normal function of human skeletal muscle, which can be used to develop therapies for affected patients.Read moreRead less
From Linkage To Genes Conferring Susceptibility To Schizophrenia: Investigation Of Candidate Genes On Chromosome 6p
Funder
National Health and Medical Research Council
Funding Amount
$462,250.00
Summary
Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genet ....Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly increasing. The identification and characterisation of genetic factors involved in brain function and dysfunction is likely to bring about novel insights into the neural and molecular mechanisms underlying schizophrenia. There is evidence, reported by several groups including our own, that genes, co-segregating with schizophrenia in families are located in a region on chromosome 6p. By fine-grain genetic dissection of this region, we and others have found that the gene coding for the protein dysbindin is associated with schizophrenia. Our aim is to identify the DNA variant(s) in the dysbindin gene, as well as variants in other candidate genes that may be located in chromosome 6p. We will use state-of-the art methods and information on genes and DNA variants, made available through the Human Genome Project. Once genetic variants are identified, we will analyse gene expression in post mortem brain tissue of persons with schizophrenia and study the distribution and function of the proteins coded by the identified genes. Our ultimate goal is to identify specific genetic factors involved in the brain dysfunction characterising schizophrenia. If successful, this should lead to clues about the causes of the disorder. In addition, the study will contribute to the development of methods for early diagnosis and prevention. Possibly, the most important outcome will be the identification of molecular targets for novel and more specific pharmacological treatments that may eventually replace current symptom-oriented antipsychotic medications.Read moreRead less