Emily, thanks for sharing the results of Jackson’s genetic studies, particularly the exome sequencing and the four genes with variants of interest that were found. I want to summarize the significant results here (at least as I understand them), and then generate a few lines of inquiry to present to any experts that might help. I don’t want it to be a whole genetics course, but I want to add enough detail so that both ourselves, and any geneticist, protein experimentalist or modeler, neurologist, neurobiologist, or radiologist clinician can get the fuller picture.
Jackson is the person the geneticists designate as the ‘proband’, meaning the one who initiated the study, in this case a one year old boy. Four variants in four genes were noted:
NEB (nebulin) c.11450G>A; p.S3817N
PLP1 (proteolipid protein 1) c.194T>G; p.I65S
ERCC6 (excision repair cross-complementation group 1) c.2924G>A; p.R975Q
PGAP1 (post-GPI attachment to proteins 1) c.2525+4C>T
Plunging an electrode deep into the brain is one way to ablate hundreds of voxels of white matter. Unfortunately, there is no ‘before and after’ imaging study that could possibly tell you where in the cortex you would find the actual neuron bodies that had their axons clipped. Pyramidal cell axons project out of the cortex and branch in the white matter to contact many potential targets -- the spinal cord, deep brain stem nuclei, and contralateral hemisphere to name a few. Compromising the business end of a few thousand random neurons might be an acceptable side effect for giving a voice to the locked-in, an arm to the paraplegic, or steadiness to the tremoring hand of a Parkinson’s victim, however, for the elective augmentative procedures many future healthy subjects will eventually want and need, it may be a deal breaker.