Neurofibromatosis 2: finding the gene (A study of teh processes involved in finding a new gene locus using NF2 as a case study)

Abstract

The Neurofibromatoses are two autosomal dominant disorders classified as Neurofibromatoses type1 (NF1) and Neurofibromatoses type2 (NF2). They are primarily neural tumours with distinct clinical and genetic characteristics even though areas of clinical similarities exist.1 Neurofibromatosis 2 is characterised by bilateral acoustic neuromas and a predisposition to the formation of tumours. The search for the NF2 gene started with observational studies of inheritance patterns in large families expressing the NF2 phenotype, which led to the realisation that NF2 is a genetic disease. The work of various groups of researchers using deletion mapping, somatic cell hybrid maps and radiation hybrid maps with linkage analysis firmly established that the NF2 gene was located in a region located on the long arm of chromosome 22 (22q11.1-q13.1); a region with several markers any of which could have been the candidate gene. With the help of further studies, including chromosomal breakpoint studies and ‘chromosome walking' techniques the NF2 region was further narrowed to a size small enough to allow for cloning of the entire NF2 region and later, sequencing of the NF2 gene. Thus the gene for Neurofibromatosis 2, a disease that was first described about 1930, was eventually discovered in 1993. This article attempts to review the processes that made the discovery of the gene possible.

Nigerian Journal of Health and Biomedical Sciences Vol. 7 (1) 2008 pp. 64-71