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Updated: May 23, 2026
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Exon skipping mutations in neurofibromatosis
Emanuele Buratti1, Diana Baralle
1Department of Molecular Pathology, ICGEB, Trieste, Italy.
Abstract:
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.
Insights
Splicing defects in pre-mRNA are a major cause of genetic diseases, particularly in the NF-1 gene. This review details methods for identifying these critical splicing alterations.
Area of Science:
- Molecular Biology
- Genetics
- Medical Genetics
Background:
- Splicing defects in pre-mRNA are a significant cause of genetic diseases, with estimates suggesting they account for at least 15% of pathogenic mutations.
- Recent advancements in clinical practice are increasing the detection of splicing abnormalities, indicating that the true prevalence may be higher.
- Certain genes, such as the Neurofibromatosis type 1 (NF-1) gene, are particularly vulnerable to splicing alterations.
Purpose of the Study:
- To review the splicing process of the NF-1 gene.
- To discuss common methodologies for identifying splicing alterations.
- To provide practical guidance for detecting aberrant pre-mRNA splicing events in the NF-1 gene.
Main Methods:
- Review of existing literature on NF-1 gene splicing.
- Description of established techniques for splicing analysis.
- Practical considerations for optimizing the identification of splicing defects.
Main Results:
- Splicing alterations account for approximately 50% of reported disease-causing mutations in the NF-1 gene.
- The NF-1 gene is highly susceptible to mutations affecting pre-mRNA splicing.
- Various methods exist for identifying splicing defects, with specific techniques being more effective for the NF-1 gene.
Conclusions:
- Splicing defects are a crucial factor in genetic diseases, with the NF-1 gene being a prime example.
- Accurate identification of splicing alterations is essential for diagnosing genetic disorders.
- This review offers practical insights into analyzing NF-1 gene splicing to improve diagnostic accuracy.
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