Breakpoint characterization of a novel NF1 multiexonic deletion: a case showing expression of the mutated allele

Neurogenetics
Francesca OrzanPaola Riva

Abstract

Neurofibromatosis type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene. Different pathogenetic mechanisms have been identified, with the majority (95%) causing intragenic lesions. Single or multiexon NF1 copy number changes occur in about 2% of patients, but little is known about the molecular mechanisms behind these intragenic deletions. We report here on the molecular characterization of a novel NF1 multiexonic deletion. The application of a multidisciplinary approach including multiplex ligation-dependent probe amplification, allelic segregation analysis, and fluorescent in situ hybridization allowed us to map the breakpoints in IVS27b and IVS48. Furthermore, the breakpoint junction was characterized by sequencing. Using bioinformatic analysis, we identified some recombinogenic motifs in close proximity to the centromeric and telomeric breakpoints and predicted the presence of a mutated messenger ribonucleic acid, which was deleted between exons 28 and 48 and encodes a neurofibromin that lacks some domains essential for its function. Through reverse transcriptase-polymerase chain reaction, the expression of the mutated allele was verified, showing the junction between exons 2...Continue Reading

References

Jul 11, 1991·Nucleic Acids Research·G F XuR White
Dec 10, 1999·Human Molecular Genetics·M O DorschnerK Stephens
Nov 18, 2000·The Journal of Biological Chemistry·K K HiattD W Clapp
Dec 26, 2001·American Journal of Medical Genetics·L FangJ P Thirion
Jan 29, 2005·Genomics·Cristina GervasiniPaola Riva
Aug 16, 2006·Biochemical and Biophysical Research Communications·Stacey L ThomasGeorge H De Vries

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Citations

Jul 21, 2015·American Journal of Human Genetics·Meng-Chang HsiaoLudwine Messiaen
Mar 1, 2011·The Journal of Molecular Diagnostics : JMD·María Carmen ValeroConcepción Hernández-Chico

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