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Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis.

Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis.

Authors :
Jacoby LB
MacCollin M
Parry DM
Kluwe L
Lynch J
Jones D
Gusella JF
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.

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