Exon Skipping Mutations in Neurofibromatosis

  • Emanuele Buratti
  • Diana BaralleEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 867)


Defects at the level of pre-mRNA splicing represent a common source of disease mutations in almost all known diseases with a genetic aetiology. In general, it is commonly accepted that 15% of all pathogenic mutations are caused by splicing defects. However, this is probably a conservative estimate since clinical practice has only recently begun to routinely assess for this types of abnormalities. Therefore, it is expected that many currently unclassified or apparently harmless genetic variants will really turn out to be splicing-affecting defects. It is also well known that some genes are more susceptible than others to alterations in their splicing processes. Among these genes, one of the most representative is the NF-1 gene. In this gene, almost 50% of all reported disease-causing mutations can be directly attributed to alterations of the pre-mRNA process. In this chapter, we review the splicing process of the NF-1 gene and the most commonly used methods to identify splicing alterations. In particular, we provide practical notes on how to perform this analysis to maximize the chance of correctly identifying aberrant pre-mRNA splicing events in this gene.

Key words

NF-1 gene Neurofibromatosis Neurofibromin Pre-mRNA splicing Minigene systems Exon skipping 



EB is supported by a European community grant (EURASNET). DB is supported by Action Medical Research grant no. SP4175, EURASNET and Cancer Research UK.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Molecular PathologyICGEBTriesteItaly
  2. 2.Human Genetics DivisionUniversity of Southampton, Southampton General HospitalSouthamptonUK

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