Surprisingly, full PLP1 gene deletions are associated with the mildest form of the hypomyelinating leukodystrophy PMD, Pelizaeus-Merzbacher disease, while rare aneuploidy events, supernumerary copies, nonsense, missense, and partial frameshift or in-frame deletions, present with severe symptoms, suggesting that over-production and production of aberrant proteins is the most severe trigger of myelin dysfunction in PMD52,94. This evidence concerns the gene PLP1 and leukodystrophy.