The Characterisation Of The Genetic Basis Of Paget's Disease Of Bone
Funder
National Health and Medical Research Council
Funding Amount
$266,402.00
Summary
Paget's disease is a bone disease in which the normal process of bone being formed and then broken down doesn't take place in the usual way. This results in bones that are enlarged, misshapen, dense and fragile. Paget's disease usually affects people of middle age or older. Although some cases are asymptomatic, Paget's disease is a major cause of bone pain and deformity. In Australia, 3-5% of people aged 40 years and over have Paget's disease. Paget's disease usually affects one of the long bone ....Paget's disease is a bone disease in which the normal process of bone being formed and then broken down doesn't take place in the usual way. This results in bones that are enlarged, misshapen, dense and fragile. Paget's disease usually affects people of middle age or older. Although some cases are asymptomatic, Paget's disease is a major cause of bone pain and deformity. In Australia, 3-5% of people aged 40 years and over have Paget's disease. Paget's disease usually affects one of the long bones in the leg, the pelvic bone, the skull or the spine. One of the most serious complications of Paget's disease is the devlopment of bone cancer. A genetic predisposition is an important factor in the development of Paget's disease. At least a quarter of patients with Paget's disease have at least one close relative with the same condition. Although it is more than 100 years since Sir James Paget first described Paget's disease, the underlying cause remains unknown. We have identified a large family with over 200 members in which there are 35 subjects affected by Paget's disease. The pattern of inheritance in this family is consistent with an autosomal dominant disorder. We have identified a discrete genetic region that is linked with the inheritance of Paget's disease in this family, indicating that a suscpetibility gene for Paget's disease lies in this region. The research program outlined in this application will refine this localisation and will define and characterise this susceptibility gene for Paget's disease. This research program is of great clinical relevance as the identification of the causative gene will open up new approaches for the treatment and prevention of this disease.Read moreRead less
Parathyroid Tumorigenesis - A Role For The Newly Identified Putative Tumour Suppressor HRPT2
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at t ....Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at the genetic level to cause this disease is, in most cases, poorly understood. In Hyperparathyroidism Jaw Tumour Syndrome (HPT-JT), one form of familial hyperparathyroidism, we and our international collaborators have recently identified mutations in the gene HRPT2 predicted to lead to loss of function of this gene. HRPT2 has no known similarities to other genes that may give hints as to its function. The overall aim of this project is to test our theory that HRPT2 has an important role in abnormal growth of parathyroid tissue that, in some cases, will lead to cancer. Further, we hypothesise that this gene will have a role in both familial and sporadic presentations of parathyroid disease. We will investigate this gene in parathyroid tumour specimens from patients with familial and sporadic disease for gene mutations and also different levels of gene expression. We will also explore a mechanism for how these mutations may function to cause disease and look at the effect of reduced HRPT2 expression on expression of thousands of other genes using a technique known as microarray analysis. The expected outcomes of this study include the identification of individuals at risk of developing cancer whose treatment will be tailored to their genetic profile. Characterisation of HRPT2, and the genes its expression influence, may lead to the identification of suitable targets for future treatment of hyperparathyroidism and its effects on bone disease.Read moreRead less