Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia

S Barresi, M Niceta, P Alfieri, V Brankovic, G Piccini, A Bruselles, M R Barone, R Cusmai, M Tartaglia, E Bertini, G Zanni

Research output: Contribution to journalArticlepeer-review


Congenital ataxias are nonprogressive neurological disorders characterized by neonatal hypotonia, developmental delay and ataxia, variably associated with intellectual disability and other neurological or extraneurological features. We performed trio-based whole-exome sequencing of 12 families with congenital cerebellar and/or vermis atrophy in parallel with targeted next-generation sequencing of known ataxia genes (CACNA1A, ITPR1, KCNC3, ATP2B3 and GRM1) in 12 additional patients with a similar phenotype. Novel pathological mutations of ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1) were found in seven patients from four families (4/24, ∼16.8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of neuronal plasticity and development. Our study expands the mutational spectrum of ITPR1-related congenital ataxia and indicates that ITPR1 gene screening should be implemented in this subgroup of ataxias.

Original languageEnglish
Pages (from-to)86-91
Number of pages6
JournalClinical Genetics
Issue number1
Publication statusPublished - Jan 2017


  • Adult
  • Amino Acid Sequence
  • Binding Sites/genetics
  • Child
  • Exome/genetics
  • Family Health
  • Female
  • Genetic Predisposition to Disease/genetics
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors/genetics
  • Lectins, C-Type/metabolism
  • Male
  • Membrane Proteins/metabolism
  • Middle Aged
  • Mutation
  • Pedigree
  • Sequence Analysis, DNA/methods
  • Sequence Homology, Amino Acid
  • Spinocerebellar Ataxias/genetics
  • Young Adult


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