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Title: Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients
Authors: Wimmer, K ×
Yao, S
Claes, K
Kehrer-Sawatzki, H
Tinschert, S
De Raedt, Thomas
Legius, Eric
Callens, T
Beiglböck, H
Maertens, O
Messiaen, Ludwine #
Issue Date: Mar-2006
Publisher: Wiley-Liss, Inc.
Series Title: Genes, Chromosomes & Cancer vol:45 issue:3 pages:265-276
Abstract: Neurofibromatosis type 1 (NF1), the most common tumor-predisposing disorder in humans, is caused by defects in the NF1 tumor-suppressor gene. Comprehensive mutation analysis applying RNA-based techniques complemented with FISH analysis achieves mutation detection rates of approximately 95% in NF1 patients. The majority of mutations are minor lesions, and approximately 5% are total gene deletions. We found 13 single- and/or multiexon deletions/duplications out of 1,050 detected mutations using our RNA-based approach in a cohort of 1,100 NF1 patients and confirmed these changes using multiplex ligation-dependent probe amplification (MLPA). With MLPA, we found another 12 novel multiexon deletion/duplications in 55 NF1 patients for whom analysis with multiple assays had not revealed a NF1 mutation, including 50 previously analyzed comprehensively. The extent of the 22 deletions and 3 duplications varied greatly, and there was no clustering of breakpoints. We also evaluated the sensitivity of MLPA in identifying deletions in a mosaic state. Furthermore, we tested whether the MLPA P122 NF1 area assay could distinguish between type I deletions, with breakpoints in low-copy repeats (NF1-LCRs), and type II deletions, caused by aberrant recombination between the JJAZ gene and its pseudogene. Our study showed that intragenic deletions and/or duplications represent only approximately 2% of all NF1 mutations. Although MLPA did not substantially increase the mutation detection rate in NF1 patients, it was a useful first step in a comprehensive mutation analysis scheme to quickly pinpoint patients with single- or multiexon deletions/duplications as well as patients with a total gene deletion who will not need full sequencing of the complete coding region.
URI: 
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Department of Human Genetics - miscellaneous
Laboratory for Neurofibromatosis Research
× corresponding author
# (joint) last author

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