Neurofibromatosis 1 Somatic Mutation Triggering Cellular Apoptosis
to Prevent Neurofibromatosis 1 Progression
Persons with ordinary, prototypical Neurofibromatosis 1 are born with
a germinal/zygotic mutation at the NF1 locus on the long arm of chromosome 17
present in all of their cells.
An NF1 germinal mutation is the “first hit,” accounting for haploinsufficiency at the NF1 locus.
The NF1 somatic mutation is the “second hit,” accounting for diploinsufficiency (deranged or
lost function of both alleles) at the NF1 locus.
The NF1 somatic mutation occurs in a variety of somatic (i.e., non-germinal) cells,
including, and especially the schwann cells (SC). I suggest that
NF1 haploinsufficiency provides the conditions for the SC (and
other cells) to develop NF1 diploinsufficiency rather than NF1
diploinsufficiency developing independently of the conditions in
which it originates.
In either case, imagine a viral analogue with an apoptosis trigger held in abeyance
unless an NF1 somatic mutation occurs in the presence of an NF1 germinal mutation or whole
gene deletion.
That is, instead of altering the feature, for example, decreasing neurofibroma
size and symptoms with MEK inhibitors, I herein suggest an approach
to preventing certain NF1 features, keying off the fact that almost
NF1 features involve somatic mutation of the cell’s NF1 wild type allele.
The NF1 phenotype, that is, the NF1 syndrome, has many elements,
not all with the same “causal relationship” to NF1 genotype.
NF1 features are elements closest in causal proximity to the genomic disturbance,
for example, neurofibromas or vertebral dysplasia.
NF1 consequences, derived from NF1 features, include
atypical neurofibromas and spinal scoliosis.
Neuro Open J. 2020; 7(1): e1-e2. doi: 10.17140/NOJ-7-e011
