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 journalArticlepeer-review

35 Scopus citations


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
Issue number11
StatePublished - Sep 13 2011

Bibliographical note

Funding Information:
Dr. Paciorkowski receives research support from the NIH/NINDS and Washington University Children's Discovery Institute. Dr. Shafrir and Dr. Hrivnak report no disclosures. Dr. Patterson serves on scientific advisory boards for the World Health Organization, Actelion Pharmaceuticals Ltd, Shire plc, Neuraltus Pharmaceuticals, Inc., and StemCells, Inc.; serves on the editorial board of the Journal of Child Neurology and as Editor, Pediatric Neurology for Up-To-Date ; and has received research support from the NIH/NINDS and Actelion Pharmaceuticals Ltd. Dr. Tennison reports no disclosures. Dr. Clark serves on the editorial advisory boards of Human Pathology and Neurobiology of Disease and receives research support from the NIH. Dr. Gomez serves on a scientific advisory board for the National Ataxia Foundation and on the speakers' bureau of Athena Diagnostics, Inc.


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