Only abnormal trafficking of the mutated protein is causative for HSP and not from its deficiency as evident by Prader–Willi syndrome (PWS) or Angelman syndrome (AS) with only one copy of the NIPA1 gene in the typical 15q11-q13 type I deletion in both PWS or AS involving breakpoints BP1 and BP3 including the four genes in the 15q11.2 BP1-BP2 region. This evidence concerns the gene IGFBP2 and hereditary spastic paraplegia.