Back to Search
Start Over
Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis.
Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis.
- Source :
-
Neurogenetics [Neurogenetics] 1999 Apr; Vol. 2 (2), pp. 101-8. - Publication Year :
- 1999
-
Abstract
- Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by formation of multiple schwannomas and meningiomas due to inactivating mutations in the NF2 tumor suppressor gene on chromosome 22. We describe a polymorphism in the 3' untranslated region of the NF2 gene that is informative in about one-third of individuals. This polymorphism permitted an assessment of the relative expression of NF2 transcripts in lymphoblastoid cell RNA from 22 unrelated NF2 patients heterozygous for a germline NF2 mutation, along with 6 schwannomatosis patients, and 14 unaffected controls. Unequal allelic expression (1.8- to 20-fold) was detected in 15 of the NF2 cases, but in none of the schwannomatosis or control individuals. Underexpression of the NF2 mutant allele was documented for all 6 nonsense or frameshift mutations, 3 of 6 splice mutations, and 1 of 4 missense mutations, which, unexpectedly, was shown to alter the NF2 transcript and create a premature stop codon. In contrast, equal expression or slight overexpression of NF2 mutant alleles was observed for 2 in-frame deletions, 2 splice alterations, and 3 missense mutations. In the remaining 5 cases, the allele representing the mutant transcript was not known. Thus, truncating NF2 mutations, which are the most frequent alterations in NF2 patients and NF2-associated tumors, were associated with underexpression of the mutant allele, whereas the less common in-frame alterations usually showed normal or slight overexpression of the mutant transcript.
- Subjects :
- Alleles
Chromosome Mapping
Codon, Terminator
Frameshift Mutation
Germ-Line Mutation
Heterozygote
Humans
Lymphocytes metabolism
Mutation, Missense
Neurofibromin 2
Restriction Mapping
Sequence Deletion
Transcription, Genetic
Chromosomes, Human, Pair 22
Genes, Neurofibromatosis 2
Loss of Heterozygosity
Membrane Proteins genetics
Mutation
Neurilemmoma genetics
Neurofibromatosis 2 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1364-6745
- Volume :
- 2
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Neurogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 10369886
- Full Text :
- https://doi.org/10.1007/s100480050060