SPAST and hereditary spastic paraplegia: These include knockouts of two genes that have been shown to cause pure dominant HSP by haploinsufficiency: for both SPAST (spastin protein, SPG4) and REEP1 (REEP1 protein, SPG31) there is progressive gait impairment, the severity of which negatively correlates with the amount of wild-type protein available [26, 41, 42].