Disease Gene Discovery And Improved Genetic Diagnosis In Neuromuscular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$473,321.00
Summary
Paediatric nerve and muscle disorders result in weakness, chronic disability and often early death. Over half of all affected children do not yet have a genetic diagnosis. This project will use advanced sequencing technology to increase genetic diagnosis rates and identify new disease-causing genes. This will result in improved patient care and a better understanding of the biological pathways altered by these disorders. It will also facilitate the identification of targets for future therapies.
Genetic Bases For Charcot-Marie-Tooth And Hereditary Sensory Type 1 Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$618,055.00
Summary
This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradua ....This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradually increasing disability eventually requiring splints and other walking aids. We propose to use the newly developed resources of the human genome project to locate the defective gene. In previous studies we have used these methods to locate the defective genes of 2 other hereditary diseases of nerve. In this study we propose to investigate a newly recognised form of CMT called intermediate CMT. Intermediate CMT has characteristics intermediate between the better known forms of CMT affecting the nerve itself (the axon) or the nerve insulation (the surrounding myelin sheath). The disorder may therefore affect both components of nerve. The affected gene may mediate communication between the nerve and its sheath. This research should give valuable insight into the mechanisms responsible for the maintenance of normal nerve. Finding the gene may therefore have relevance to many other diseases of nerve. This research is a systematic search and should lead to the abnormal gene causing the disease. Once the gene involved is known then an effective test will be developed. When we can test for the disease, we probably will find that the disorder is much more common than previously recognised. Knowledge of the function of this gene will lead to an understanding of how the disease develops and will eventually lead to effective treatments.Read moreRead less
Gene Identification For Inherited Peripheral Neuropathies By Applying Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$605,058.00
Summary
Our goal is to study the biology underlying the death of motor and sensory nerves by identifying novel genes causing Charcot-Marie-Tooth (CMT) neuropathy. Using massively parallel sequencing we will systematically analyse the novel DNA changes througout the genome in CMT families in which the underlying gene mutation is unknown. Discovery of genes causing inherited peripheral neuropathies will elucidate mechanisms causing neurodegeneration and lead to targeted therapeutic treatment strategies to ....Our goal is to study the biology underlying the death of motor and sensory nerves by identifying novel genes causing Charcot-Marie-Tooth (CMT) neuropathy. Using massively parallel sequencing we will systematically analyse the novel DNA changes througout the genome in CMT families in which the underlying gene mutation is unknown. Discovery of genes causing inherited peripheral neuropathies will elucidate mechanisms causing neurodegeneration and lead to targeted therapeutic treatment strategies to prevent the death of motor and sensory nerves.Read moreRead less
Molecular Genetics Of Hereditary Motor And Sensory Neuropathy With Pyramidal Signs
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
This project aims to determine the molecular cause of hereditary motor neuropathies with pyramidal signs by chromosomal linkage studies and to screen suitable families to locate genes with disease causing mutations. We propose to use the resources of the human genome project to locate the defective gene. In previous studies we have used these methods to identify genes of two other hereditary diseases of nerve. Our data suggests that this disorder forms part of the largest group of hereditary neu ....This project aims to determine the molecular cause of hereditary motor neuropathies with pyramidal signs by chromosomal linkage studies and to screen suitable families to locate genes with disease causing mutations. We propose to use the resources of the human genome project to locate the defective gene. In previous studies we have used these methods to identify genes of two other hereditary diseases of nerve. Our data suggests that this disorder forms part of the largest group of hereditary neuropathies yet to be defined. Because this disorder affects long spinal cord neurones, identifying the mutated gene and studying its function may shed light on possible mechanisms involved in other spinal cord diseases. This research is a systematic search and should lead to identifying the abnormal gene causing disease. Once the gene involved is known then an effective diagnostic test will be developed. When a test for the disease is available, it is likely that we will find that the disorder is more common than previously recognised. Knowledge of the function of the gene will lead to an understanding of how the disease develops and will eventually enable development of effective treatments.Read moreRead less