Human Genetics

, Volume 99, Issue 1, pp 88–92

Mutational and functional analysis of the neurofibromatosis type 1 (NF1) gene

  • M. Upadhyaya
  • Michael J. Osborn
  • Julie Maynard
  • Mee Rhan Kim
  • Fuyuhiko Tamanoi
  • David N. Cooper
Original investigation

DOI: 10.1007/s004390050317

Cite this article as:
Upadhyaya, M., Osborn, M., Maynard, J. et al. Hum Genet (1996) 99: 88. doi:10.1007/s004390050317

Abstract

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders. It is caused by mutations in the NF1 gene which comprises 60 exons and is located on chromosome 17q. The NF1 gene product, neurofibromin, displays partial homology to GTPase-activating protein (GAP). The GAP-related domain (GRD), encoded by exons 20–27a, is the only region of neurofibromin to which a biological function has been ascribed. A total of 320 unrelated NF1 patients were screened for mutations in the GRD-encoding region of the NF1 gene. Sixteen different lesions in the NF1 GRD region were identified in a total of 20 patients. Of these lesions, 14 are novel and together comprise three missense, two nonsense and three splice site mutations plus six deletions of between 1 and 4 bp. The effect of one of the missense mutations (R1391S) was studied by in vitro expression of a site-directed mutant and GAP activity assay. The mutant protein, R1391S, was found to be some 300-fold less active than wild-type NF1 GRD. The mutations reported in this study therefore provide further material for the functional analysis of neurofibromin as well as an insight into the mutational spectrum of the NF1 GRD.

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • M. Upadhyaya
    • 1
  • Michael J. Osborn
    • 1
  • Julie Maynard
    • 1
  • Mee Rhan Kim
    • 2
  • Fuyuhiko Tamanoi
    • 2
  • David N. Cooper
    • 1
  1. 1.Institute of Medical Genetics, Heath Park, Cardiff CF4 4XN, UK Tel.: +44 1222 744081; Fax: +44 1222 747603GB
  2. 2.Department of Microbiology and Molecular Genetics, University of California, Los Angeles, USAUS