This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this work is to assess the NF1 gene in individuals and their family members with neurofibromatosis (NF1) or suspected of having NF1. Assessing the mutations in NF1 genes is part of a larger project on the study of cancer and mortality in NF1 by genotype. Each patient will have a clinical evaluation at Children's Hospital of Oklahoma or elsewhere. During the visit the patients will receive counseling about NF1 and the risk and benefits of gene testing. This study will help us correlate specific mutations in the NF1 gene with specific phenotypes. The results may help the health care providers determine the risks of developing certain clinical features of NF1, which can lead to improved education and counseling concerning psychosocial factors, prognostic and other concerns of NF1 patients. A genotype-phenotype correlation could also help to introduce new therapies and interventions, and the effectiveness of genetic screening in predicting the disease and the outcome in the children of people with NF1. Improvements of a gene test for NF1 may be useful for ruling in or out a suspected diagnosis of NF1. We hypothesize that no mutation within the NF1 gene is associated with a specific endpoint, such as early death, a specific cancer, or any other medical event and that such events, in fact, show no significant clustering within families. The expected result is that at least one mutation, region of mutation, or class of mutation will appear to be associated with a certain endpoint, such as those families with NF1 that have an apparent excess of cancer. The work of the NIH grant parent that partly supports this gene assay has three specific aims.
Specific Aim 1 - To determine the specific mutation within the NF1 gene in individuals and their family members.
Specific Aim 2 - To explore possible NF1 mutation-specific associations with certain phenotypes.
Specific Aim 3 - To assay the clinical validity of NF1 gene testing. During the clinical evaluation of study volunteers, we will usually construct a family tree, obtain medical history, and conduct targeted physical examination for diagnostic criteria of NF1. With the patient's (or parents') consent, we will request a blood sample for testing for NF1 mutations by a protein truncation assay, single-stranded conformation polymorphism gels, automatic fluorescent sequencing, RT-PCR, or other methods. The incidence of specific phenotypes will be compared by NF1 genotype. Buccal swabs may be an alternative source of DNA.
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