Human Molecular Genetics, Vol 7, 335-345, Copyright © 1998 by Oxford University Press
DH Gutmann, RT Geist, Hm Xu, JS Kim and S Saporito-Irwin
Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from
mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has
revealed some general genotype-phenotype correlations. Severe disease has
been associated with mutations that produce a premature termination while
more mild disease has been associated with missense mutations. Here, we
provide experimental proof for these genotype-phenotype correlations by
demonstrating that nonsense mutations fail to produce stable merlin protein
while missense mutations result in the generation of merlin proteins
defective in negative growth regulation. This inability to suppress cell
growth may result from defects in the function of merlin at several levels,
including failure to form an intramolecular complex. Based on these
findings, we propose a model for merlin growth suppression that provides a
framework for analyzing NF2 patient mutations and merlin function.
ARTICLES
Defects in neurofibromatosis 2 protein function can arise at multiple levels
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA. gutmannd@neuro.wustl.edu
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