title: NF2 gene in neurofibromatosis type 2 patients.
abstract: Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that predisposes to nervous system tumors. The schwannomin (also termed merlin) protein encoded by the NF2 gene shows a close relationship to the family of cytoskeleton-to-membrane proteins linkers ERM (ezrin-radixin-moesin proteins). Even though penetrance of the disease is >95% and no genetic heterogeneity has been described, point mutations in the NF2 gene have been observed in only 34-66% of the screened NF2 patients, depending on the series. In order to generate tools that would enable an exhaustive alteration screening for the NF2 gene, we have deduced its entire genomic sequence. This knowledge has provided the delineation of a mutation screening strategy which, when applied to a series of 19 NF2 patients, has revealed a high recurrence of large deletions in the gene and has raised the efficiency of mutation detection in NF2 patients to 84% of the cases in this series. The remaining three patients who express two functional NF2 alleles are all sporadic cases, an observation compatible with the presence of mosaicism for NF2 mutation.
authors.affiliation: Laboratoire de génétique des tumeurs, INSERM U434 and CEPH/ Fondation Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France. zucman@cephb.fr
authors.forename: J
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: P
authors.initials: P
authors.lastname: Legoix
authors.forename: H
authors.initials: H
authors.lastname: Der Sarkissian
authors.forename: G
authors.initials: G
authors.lastname: Cheret
authors.forename: F
authors.initials: F
authors.lastname: Sor
authors.forename: A
authors.initials: A
authors.lastname: Bernardi
authors.forename: L
authors.initials: L
authors.lastname: Cazes
authors.forename: S
authors.initials: S
authors.lastname: Giraud
authors.forename: E
authors.initials: E
authors.lastname: Ollagnon
authors.forename: G
authors.initials: G
authors.lastname: Lenoir
authors.forename: G
authors.initials: G
authors.lastname: Thomas
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005091:Exons; D015321:Gene Rearrangement; D016515:Genes, Neurofibromatosis 2 / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D016518:Neurofibromatosis 2 / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012313:RNA / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D012313:RNA; D004247:DNA