Mutational analysis of patients with neurofibromatosis 2.
- 1 August 1994
- journal article
- Vol. 55 (2) , 314-20
Abstract
Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecular basis of NF2 in affected individuals, we have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. We conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare.This publication has 17 references indexed in Scilit:
- The murine NF2 homologue encodes a highly conserved merlin protein with alternative formsHuman Molecular Genetics, 1994
- Exon scanning for mutation of the NF2 gene in schwannomasHuman Molecular Genetics, 1994
- Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour typesNature Genetics, 1994
- Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomasNature Genetics, 1994
- DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the merlin tumor suppressor in an extended pedigreePublished by American Medical Association (AMA) ,1993
- ErrataCell, 1993
- Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2Nature, 1993
- A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressorCell, 1993
- Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reactionGenomics, 1989
- Neurofibromatosis 2New England Journal of Medicine, 1988