Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms

A. R. Paciorkowski, Y. Shafrir, J. Hrivnak, M. C. Patterson, M. B. Tennison, H. B. Clark, C. M. Gomez

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1055-1060
Number of pages6
JournalNeurology
Volume77
Issue number11
DOIs
StatePublished - Sep 13 2011
Externally publishedYes

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Spinocerebellar Ataxias
Infantile Spasms
Retinitis Pigmentosa
Computational Biology
Brain Diseases
Endocytosis
Proteins
Muscle Hypotonia
Phenotype
Protein
Bioinformatics
Genes
Pathway
Interaction

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Paciorkowski, A. R., Shafrir, Y., Hrivnak, J., Patterson, M. C., Tennison, M. B., Clark, H. B., & Gomez, C. M. (2011). Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. Neurology, 77(11), 1055-1060. https://doi.org/10.1212/WNL.0b013e31822e5627

Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. / Paciorkowski, A. R.; Shafrir, Y.; Hrivnak, J.; Patterson, M. C.; Tennison, M. B.; Clark, H. B.; Gomez, C. M.

In: Neurology, Vol. 77, No. 11, 13.09.2011, p. 1055-1060.

Research output: Contribution to journalArticle

Paciorkowski, AR, Shafrir, Y, Hrivnak, J, Patterson, MC, Tennison, MB, Clark, HB & Gomez, CM 2011, 'Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms', Neurology, vol. 77, no. 11, pp. 1055-1060. https://doi.org/10.1212/WNL.0b013e31822e5627
Paciorkowski AR, Shafrir Y, Hrivnak J, Patterson MC, Tennison MB, Clark HB et al. Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. Neurology. 2011 Sep 13;77(11):1055-1060. https://doi.org/10.1212/WNL.0b013e31822e5627
Paciorkowski, A. R. ; Shafrir, Y. ; Hrivnak, J. ; Patterson, M. C. ; Tennison, M. B. ; Clark, H. B. ; Gomez, C. M. / Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and infantile spasms. In: Neurology. 2011 ; Vol. 77, No. 11. pp. 1055-1060.
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