Detecting Missing Heritability for Risk Stratification and Clinical Management of the Neurofibromatoses
Abstract
Neurofibromatosis type 1 (NF1), Neurofibromatosis type 2 (NF2), and schwannomatosis diseases cause people to develop tumours in their brain and on the nerves throughout their body. While each of these conditions is different at a genetic level and has different associated health risks, sometimes it is difficult for doctors to tell them apart when patients first present with symptoms. In these cases, it is particularly important to be able to distinguish the disorders using gene testing, as misclassification can lead to delays in appropriate treatment. Genetic testing often leads to an accurate diagnosis. However, in some cases, it is still not possible to find a disease-causing mutation using routine genetic tests currently offered through our National Health Service. We aim to determine the usefulness of more in-depth genetic testing strategies in people whose mutation has not been found through routine testing. Our clinical service in Manchester has tested a large number of people with these disorders, and we have identified some cases in whom no gene change has been found to explain their disease. We will use a combination of traditional and recently developed genetic testing methods on samples from these people to develop improved screening strategies that can then be made available for patients with these disorders. This information will help people who may have NF1, NF2, or schwannomatosis, but who do not have a known disease-causing mutation to explain why they have developed tumours. Accurate genetic diagnosis of these disorders and knowledge of the likely risk of tumours associated with their specific mutation will help to guide doctors and other healthcare professionals to provide accurate information on disease risk and appropriate treatment options. It would also allow detection of disease risk in family members and aid family planning decisions. We expect that, during the project funding period, we will be able to find new types of disease-causing mutation in the genes that are already known to be associated with disease. We also plan to look for new genes associated with schwannomatosis, since our previous research has shown that further genes remain to be discovered for this form of disease. Overall, we expect that the results of our study will help to improve medical care for patients with NF1, NF2, and schwannomatosis whose disease-causing gene change has not yet been found. They will also be helpful to their family members, who can be tested to see whether they are also at risk of disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910334
Entities
People
- Miriam J Smith
Organizations
- United States Army
- University of Manchester