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

Maria Lisa Dentici, Sabina Barresi, Marta Nardella, Emanuele Bellacchio, Paolo Alfieri, Alessandro Bruselles, Francesca Pantaleoni, Alberto Danieli, Giancarlo Iarossi, Marco Cappa, Enrico Bertini, Marco Tartaglia, Ginevra 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.
Original languageEnglish
Pages (from-to)141-145
Number of pages5
Publication statusPublished - Sep 10 2017


  • Cerebellar atrophy
  • Inositol 1,4,5 tri-phosphate receptor (InsP3) type 1 (ITPR1)
  • Intellectual disability
  • Partial aniridia


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