disease 3,014 words KG: ent-dise-add555c8
Contents

spinocerebellar-ataxia-type-2

Disease Info
CAG repeat expansionPathogenic mutation is an expanded CAG trinucleotide repeat in the ATXN2 gene on chromosome 12q24.1
Normal alleles13-31 CAG repeats
Intermediate alleles32-33 repeats (may be unstable)
Full mutation alleles34-200+ repeats (disease-causing)
AnticipationLarger repeats are associated with earlier onset, particularly through paternal transmission
Normal functionAtaxin-2 interacts with multiple RNA-binding proteins and is involved in translational control
Pathogenic mechanismThe expanded polyglutamine tract causes toxic gain-of-function, leading to RNA metabolism dysregulation and cellular stress
Expression patternWidely expressed in the central nervous system, with high levels in Purkinje cells and cerebellar nuclei
Cerebellar degenerationSevere loss of Purkinje cells throughout the cerebellar cortex
Inferior olivary nucleus degenerationProminent neuronal loss in the inferior olive
Brainstem pathologyDegeneration of the pons and midbrain nuclei
Basal ganglia involvementVariable involvement of the striatum and subthalamic nucleus
DatabasesOMIMOrphanetClinicalTrialsPubMed

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