title: Molecular characterization of germline NF2 gene rearrangements.
abstract: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease that causes a predisposition to nervous system tumors. Deleterious point mutations have been found in about 55% of NF2 patients, and large genomic deletions account for approximately 33% of NF2 gene alterations. The majority of these deletions are larger than 50 kb, with a breakpoint usually lying outside the NF2 gene. We identified two cases of intragenic deletion with loss of 1.5 and 40 kb, respectively. In both cases, one boundary of the deletion was located in or at the proximity of an SVA sequence in NF2 intron 4. No sequence identity longer than 5 bases and no signal of specific recombination have been evidenced on either side of the deletion breakpoints. These observations are compatible with a nonhomologous recombination being responsible for the genomic deletions. In a third case, a paracentric inversion of chromosome 22 was found. This chromosomal rearrangement breaks the NF2 gene in two parts and carries the first NF2 exon in a juxta-centromeric position. The variability in position of the deletions and the observation of a new chromosomal rearrangement in the NF2 gene underscore the importance of FISH analysis in the molecular diagnosis of NF2.
authors.affiliation: Laboratoire de génétique des tumeurs, INSERM U434, Fondation Jean Dausset, CEPH, 27 rue Juliette Dodu, Paris, 75010, France.
authors.forename: P
authors.initials: P
authors.lastname: Legoix
authors.forename: H D
authors.initials: HD
authors.lastname: Sarkissian
authors.forename: L
authors.initials: L
authors.lastname: Cazes
authors.forename: S
authors.initials: S
authors.lastname: Giraud
authors.forename: F
authors.initials: F
authors.lastname: Sor
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: G
authors.initials: G
authors.lastname: Lenoir
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Zucman-Rossi
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016518:Neurofibromatosis 2 / Q000235:genetics*; D025581:Neurofibromin 2; D012689:Sequence Homology, Nucleic Acid
chemical_list: D008565:Membrane Proteins; D025581:Neurofibromin 2; D004247:DNA