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.
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: Tania Cruz-Mariño; Luis Velázquez-Pérez; Yanetza González-Zaldivar; Raúl Aguilera-Rodríguez; Miguel Velázquez-Santos; Yaimé Vázquez-Mojena; Annelié Estupiñán-Rodríguez; Rubén Reynaldo-Armiñán; Luis Enrique Almaguer-Mederos; José Miguel Laffita-Mesa; Victor Tamayo-Chiang; Milena Paneque Journal: J Community Genet Date: 2013-05-15
Authors: José Miguel Laffita-Mesa; Jorge Michel Rodríguez Pupo; Raciel Moreno Sera; Yaimee Vázquez Mojena; Vivian Kourí; Leonides Laguna-Salvia; Michael Martínez-Godales; José A Valdevila Figueira; Peter O Bauer; Roberto Rodríguez-Labrada; Yanetza González Zaldívar; Martin Paucar; Per Svenningsson; Luís Velázquez Pérez Journal: PLoS One Date: 2013-08-06 Impact factor: 3.240
Authors: Chad A Sundberg; Monika Lakk; Sharan Paul; Karla P Figueroa; Daniel R Scoles; Stefan M Pulst; David Križaj Journal: J Comp Neurol Date: 2021-08-18 Impact factor: 3.215