title: Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms.
abstract: OBJECTIVE
  To provide clinical data on a cohort of 6 patients with massive expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and investigate possible pathways of pathogenesis using bioinformatics analysis of ATXN2 networks.
  
  
  METHODS
  We present data on 6 patients with massive expansion of SCA2 who presented in infancy with variable combinations of hypotonia, global developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known to interact with a network of synaptic proteins. To investigate pathways of pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known genes associated with infantile spasms, retinitis pigmentosa, and synaptic function.
  
  
  RESULTS
  All patients had a progressive encephalopathy with autonomic dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The bioinformatics analysis led to several interesting findings. First, an interaction between ATXN2 and SYNJ1 may account for the development of retinitis pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be important in children with this progressive encephalopathy. Infantile spasms may be associated with interactions between ATXN2 and the postsynaptic structural proteins MAGI2 and SPTAN1.
  
  
  CONCLUSIONS
  Severe phenotype in children with massive expansion of SCA2 may be due to a functional deficit in protein networks in the postsynapse, specifically involving vesicle endocytosis.
authors: Department of Neurology, Washington University, St. Louis, MO, USA. arpac@u.washington.edu
authors: A R
authors: AR
authors: Paciorkowski
authors: Y
authors: Y
authors: Shafrir
authors: J
authors: J
authors: Hrivnak
authors: M C
authors: MC
authors: Patterson
authors: M B
authors: MB
authors: Tennison
authors: H B
authors: HB
authors: Clark
authors: C M
authors: CM
authors: Gomez
mesh_terms: D000067528:Ataxins; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D057907:Post-Synaptic Density / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins