Exon scanning for mutation of the NF2 gene in schwannomas

Family studies and tumor analyses have combined to indicate that neurofibromatosls 2 (NF2), a disorder characterized by multiple benign tumors of the nervous system, and sporadic non-Inherited forms of the same tumor types are both caused by inactlvation of a tumor suppressor gene located in 22q12....

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Bibliographic Details
Published in:Human molecular genetics 1994-03, Vol.3 (3), p.413-419
Main Authors: Jacoby, Lee B., MacCollin, Mia, Louls, David N., Mohney, Trina, Rublo, Mari-Paz, Pulaski, Karen, Trofatter, James A., Kley, Nikolai, Seizinger, Bernd, Ramesh, Vijaya, Gusella, James F.
Format: Article
Language:English
Subjects:
Alternative Splicing
Base Sequence
Biological and medical sciences
DNA
Exons
Genes, Neurofibromatosis 2
Humans
Introns
Medical sciences
Membrane Proteins - genetics
Molecular Sequence Data
Mutation
Neoplasm Proteins - genetics
Neurilemmoma - genetics
Neurofibromin 2
Neurology
Polymerase Chain Reaction
Polymorphism, Genetic
Tumors of the nervous system. Phacomatoses
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Summary:Family studies and tumor analyses have combined to indicate that neurofibromatosls 2 (NF2), a disorder characterized by multiple benign tumors of the nervous system, and sporadic non-Inherited forms of the same tumor types are both caused by inactlvation of a tumor suppressor gene located in 22q12. Recently, the gene encoding merlin, a novel member of a family of cytoskeleton-associated proteins, was Identified as the NF2 tumor suppressor. To facilitate the search for merlin mutations, we have defined the exon-intron boundaries for all 17 NF2 exons, including one subject to alternative splicing. We have developed polymerase chain reaction assays to amplify each exon from genomlc DNA, and used these assays to perform single-strand conformation polymorphism analysis of DNA from 30 sporadic and eight NF2-derlved schwannomas, the hallmark tumor type In this disorder. Of a maximum of 60 alleles scanned, 32 showed mutations affecting expression of the merlin protein. Thirty of these mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal splicing, while two are missense mutations. Thus, Inactivation of merlin is a common feature underlying both Inherited and sporadic forms of schwannoma.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/3.3.413