Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes
Viviana Tritto1, Marica Eoli2, Rosina Paterra2
1Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, 20054 Segrate, Italy.
International Journal of Molecular Sciences
|September 9, 2022
Summary
Neurofibromatosis type 2 (NF2) patients with 22q12 microdeletions show varied symptoms. Deletion size correlates with NF2 phenotype severity, offering prognostic insights and potential therapeutic targets.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder linked to NF2 gene mutations.
- 22q12 microdeletions are rarely described in NF2, with unknown pathogenic mechanisms.
- Understanding the genetic and epigenetic impact of 22q12 microdeletions is crucial for NF2 management.
Purpose of the Study:
- To characterize 22q12 microdeletions in three NF2 patients with complex phenotypes.
- To investigate the genotype-phenotype correlation based on deletion size and location.
- To explore the potential genetic and epigenetic effects of these microdeletions.
Main Methods:
- Whole-genome sequencing and in silico analysis of topologically associated domains (TADs).
- Analysis of regulatory elements and gene expression of flanking genes.
- Correlation of deletion extent with clinical phenotype complexity.
Main Results:
- Identified microdeletions ranging from 147 Kb to 1.8 Mb, correlating with NF2 phenotype severity.
- Observed intellectual disability in patients with larger deletions, potentially linked to AP1B1 deletion.
- Detected altered expression of four flanking genes (e.g., PIK3IP1) and association with early ischemic events.
Conclusions:
- Deletion extent serves as a prognostic marker for NF2 phenotypes.
- 22q12 microdeletions impact gene expression and chromatin landscape, influencing disease presentation.
- Characterization of microdeletions can guide therapeutic strategies and improve patient management.
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