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Screening for germ‐line mutations in the NF2 Gene
Author(s) -
Mérel Philippe,
HoangXuan Khé,
Sanson Marc,
Bijlsma Emilia,
Rouleau Guy,
LaurentPuig Pierre,
Pulst Stephan,
Baser Michael,
Lenoir Gilbert,
Sterkers Jean Marc,
Philippon Jacques,
Resche François,
Mautner Victor F.,
Fischer Georges,
Hulsebos Theo,
Aurias Alain,
Delattre Olivier,
Thomas Gilles
Publication year - 1995
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870120206
Subject(s) - biology , genetics , gene , exon , point mutation , mutation , intron , neurofibromatosis type 2 , gene mutation , coding region , neurofibromatosis , phenotype , tumor suppressor gene , microbiology and biotechnology , carcinogenesis
Neurofibromatosis type 2 (NF2) is a monogenic dominantly inherited disease that predisposes to the development of tumors of the nervous system, particularly meningiomas and schwannomas. The gene which, when altered, causes NF2, is localized on chromosome 22 and has recently been identified. The NF2 gene is also the site of somatic mutation in tumors, suggesting that it might have a tumor suppressor activity. We here report a screening method for the detection of point mutations in NF2 which takes advantage of denaturing gradient gel electrophoresis (DGGE). This method efficiently screens 95% of the coding sequence and 90% of intron/exon junctions. When applied to 91 unrelated NF2 patients, it enabled the identification of 32 germ‐line mutations. Since mutations are found in only one third of the patients, it is expected that mutations or deletions affecting the promoter and/or intronic regions of the NF2 gene occur frequently. The characterized mutations are preferentially located within the 5° half of the gene. Most of them are predicted to lead to the synthesis of a truncated protein. A search for genotype/phenotype correlations showed that, at least in this series of patients, mild manifestations of the disease were associated with mutations which preserve the C‐terminal end of the protein.