title: Uncommon Alu-mediated NF1 microdeletion with a breakpoint inside the NF1 gene.
abstract: Neurofibromatosis type 1 (NF1) microdeletion syndrome is caused by haploinsufficiency of the NF1 gene and of gene(s) located in adjacent flanking regions. Most of the NF1 deletions originate by nonallelic homologous recombination between repeated sequences (REP-P and -M) mapped to 17q11.2, while a few uncommon deletions show unusual breakpoints. We characterized an uncommon 1.5-Mb deletion of an NF1 patient displaying a mild phenotype. We applied high-resolution FISH analysis allowing us to obtain the sequence of the first junction fragment of an uncommon deletion showing the telomeric breakpoint inside the IVS23a of the NF1 gene. Sequence analysis of the centromeric and telomeric boundaries revealed that the breakpoints were present in the AluJb and AluSx regions, respectively, showing 85% homology. The centromeric breakpoint is localized inside a chi-like element; a few copies of this sequence are also located very close to both breakpoints. The in silico analysis of the breakpoint intervals, aimed at identifying consensus sequences of several motifs usually involved in deletions and translocations, suggests that Alu sequences, probably associated with the chi-like element, might be the only recombinogenic motif directly mediating this large deletion.
authors.affiliation: Department of Biology and Genetics, Medical Faculty, University of Milan, via Viotti 3/5, 20133 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasini
authors.forename: Marco
authors.initials: M
authors.lastname: Venturin
authors.forename: Francesca
authors.initials: F
authors.lastname: Orzan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Friso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.forename: Romano
authors.initials: R
authors.lastname: Tenconi
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.forename: Paola
authors.initials: P
authors.lastname: Riva
mesh_terms: D020087:Alu Elements; D001483:Base Sequence; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009456:Neurofibromatosis 1 / Q000235:genetics*; D017384:Sequence Deletion