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 χ-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 χ-like element, might be the only recombinogenic motif directly mediating this large deletion.

Uncommon Alu-mediated NF1 microdeletion with a breakpoint inside the NF1 gene / C. Gervasini, M. Venturin, F. Orzan, A. Friso, M. Clementi, R. Tenconi, L. Larizza, P. Riva. - In: GENOMICS. - ISSN 0888-7543. - 85:2(2005), pp. 273-279. [10.1016/j.ygeno.2004.10.014]

Uncommon Alu-mediated NF1 microdeletion with a breakpoint inside the NF1 gene

C. Gervasini
Primo
;
M. Venturin
Secondo
;
F. Orzan;L. Larizza
Penultimo
;
P. Riva
Ultimo
2005

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 χ-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 χ-like element, might be the only recombinogenic motif directly mediating this large deletion.
χ-like element; Alu sequences; Breakpoint junction; Uncommon NF1 microdeletion
Settore BIO/13 - Biologia Applicata
Settore MED/03 - Genetica Medica
2005
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/17167
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