Autosomal-dominant early-onset spastic paraparesis with brain calcification due to IFIH1 gain-of-function.

ABSTRACT: We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon-stimulated gene transcripts was recorded in all three affected individuals and in two clinically unaffected relatives. A heterozygous IFIH1 c.2544T>G missense variant (p.Asp848Glu) segregated with interferon status. Although not highly conserved (CADD score 10.08 vs. MSC-CADD score of 19.33) and predicted as benign by in sil

SUBMITTER: Ruaud L 

PROVIDER: S-EPMC6043383 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature