ALS2 and amyotrophic lateral sclerosis: The mutation frequency of ALS-associated genes has been recently found to be similar in sporadic PMA and ALS cases [27], and several minor ALS-associated genes such as ALS2, SETX, FIG4, OPTN, UBQLN2, and SPG11 have been consistently associated with UMN predominant phenotypes [28], suggesting a significant genetic overlap between these clinically diverse syndromes.