Background   @entity9718 is a neurodegenerative phenotype characterized by a progressive loss of corticospinal motor tract function. In a majority of affected individuals the pathogenesis remains undetermined. Methods   We identified a series of @entity1 with a phenotype of nonsyndromic @entity451 in whom no diagnosis had been reached before exome sequencing. We measured the expression of interferon stimulated genes (ISGs) in peripheral blood from these @entity1 . Results   Five @entity1 from four families with previously unexplained @entity451 were identified with mutations in either @entity39861 (one @entity1 ), @entity10465 (one @entity1 ), or @entity56597 (three @entity1 from two families). All @entity1 were developmentally normal before the onset of features beginning in the second year of life. All @entity1 remain of normal intellect. Four @entity1 demonstrated normal neuroimaging, while a single @entity1 had features of nonspecific @entity17 . The @entity1 with @entity39861 and @entity10465 -related disease showed a robust interferon signature. The @entity1 with mutations in @entity56597 demonstrated no (two @entity1 ) or a minimal (one @entity1 ) upregulation of ISGs compared with controls. Conclusions   Mutations in @entity39861 , @entity10465 , and @entity56597 can cause a phenotype of @entity451 with normal neuroimaging, or in association with nonspecific @entity17 . Although the presence of an interferon signature can be helpful in interpreting the significance of gene variants in this context, @entity1 with pathogenic mutations in @entity56597 may demonstrate no upregulation of ISGs in peripheral blood. However, it remains possible that type I interferons act as a neurotoxin in the context of all genotypes.

Mutations in @entity39861 , @entity10465 , and @entity56597 Presenting As XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity9718 :: ('MESH:D015419', 'Disease') :: ['Hereditary spastic paraplegia'] @entity17 :: ('MESH:D003711', 'Disease') :: ['dysmyelination'] @entity56597 :: ('79621', 'Gene') :: ['RNASEH2B'] @entity39861 :: ('103', 'Gene') :: ['ADAR1'] @entity451 :: ('MESH:C536857', 'Disease') :: ['spastic paraplegia'] @entity10465 :: ('64135', 'Gene') :: ['IFIH1']
@entity451 :: (MESH:C536857,Disease) :: ['Spastic Paraplegia']
