Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome

M.L. Dentici, S. Barresi, M. Nardella, E. Bellacchio, P. Alfieri, A. Bruselles, F. Pantaleoni, A. Danieli, G. Iarossi, M. Cappa, E. Bertini, M. Tartaglia, G. Zanni

Research output: Contribution to journalArticlepeer-review


ITPR1 encodes an intracellular receptor for inositol 1,4,5-trisphosphate (InsP3) which is highly expressed in the cerebellum and is involved in the regulation of Ca2 + homeostasis. Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy. Gillespie syndrome is characterized by congenital ataxia, mild to moderate intellectual disability and iris hypoplasia. Dominant or recessive ITPR1 mutations have been recently associated with this form of syndromic ataxia. We performed next generation sequencing in two simplex families with Gillespie syndrome and identified de novo pathological mutations localized in the C-terminal channel domain of ITPR1 in both patients: a recurrent deletion (p.Lys2596del) and a novel missense mutation (p.Asn2576Ile) close to a point of constriction in the Ca2 + pore. Our study expands the mutational spectrum of ITPR1 and confirms that ITPR1 screening should be implemented in patients with congenital cerebellar ataxia with or without iris hypoplasia. © 2017 The Authors
Original languageEnglish
Pages (from-to)141-145
Number of pages5
Publication statusPublished - 2017


  • Cerebellar atrophy
  • Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1)
  • Intellectual disability
  • Partial aniridia
  • adult
  • Article
  • case report
  • cerebellar ataxia
  • child
  • clinical article
  • clinical feature
  • female
  • gene
  • gene deletion
  • gene mutation
  • Gillespie syndrome
  • human
  • hydrogen bond
  • hypoplasia
  • inositol 1,4,5 trisphosphate receptor type 1 gene
  • intellectual impairment
  • iris hypoplasia
  • missense mutation
  • neuroimaging
  • neuropsychological test
  • next generation sequencing
  • preschool child
  • priority journal
  • protein function
  • Sanger sequencing
  • slit lamp
  • visual acuity
  • visual evoked potential
  • Wechsler adult intelligence scale
  • aniridia
  • dna mutational analysis
  • genetics
  • mutation
  • inositol 1,4,5 trisphosphate receptor
  • ITPR1 protein, human
  • Adult
  • Aniridia
  • Cerebellar Ataxia
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Gene Deletion
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors
  • Intellectual Disability
  • Mutation
  • Mutation, Missense


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