Abstract
Among genomic disorders, submicroscopic deletions underlying neurofibromatosis 1 (NF1) are unusual because they involve the deletion of a tumor suppressor gene (NF1), they show a different preference for low-copy repeats (LCR) as substrates for meiotic vs mitotic recombination events, and they account for only a small fraction of mutations that cause the disorder. The NF1 gene at chromosome 17q1 1.2 is flanked by two sets of LCRs in direct orientation that undergo paralogous recombination. A pair of NF1-REPs mediate the recurrent constitutional 1.4-Mb microdeletion that occurs preferentially during maternal meiosis, whereas a pair of JJAZ1 pseudogene and functional gene mediate the recurrent 1.2-Mb microdeletion that occurs preferentially during postzygotic mitosis in females. Breakpoints have been mapped at the nucleotide level for both deletions and sequence features that may contribute to the choice of discrete sites for strand exchange have been identified. NF1 -REP-mediated NF1 microdeletions involve 13 additional genes, whereas JJAZ1 -mediated microdeletions involve the same genes but one. NF1 microdeletions are of great interest because they predispose to a heavy tumor burden, malignancy, and possibly other severe manifestations.
Keywords
- Malignant Peripheral Nerve Sheath Tumor
- Neurofibromatosis Type
- Somatic Mosaicism
- Mitotic Recombination
- Short Intersperse Nuclear Element
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© 2006 Humana Press Inc., Totowa, NJ
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Stephens, K. (2006). Neurofibromatosis 1. In: Lupski, J.R., Stankiewicz, P. (eds) Genomic Disorders. Humana Press. https://doi.org/10.1007/978-1-59745-039-3_14
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