Additional features of Gillespie syndrome in two Brazilian siblings with a novel ITPR1 homozygous pathogenic variant

Eur J Med Genet. 2018 Mar;61(3):134-138. doi: 10.1016/j.ejmg.2017.11.005. Epub 2017 Nov 21.


Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.

Keywords: Aniridia; Cerebellar ataxia; Gillespie syndrome; ITPR1; Intellectual disability.

Publication types

  • Case Reports

MeSH terms

  • Aniridia / genetics*
  • Aniridia / pathology*
  • Brazil
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / pathology*
  • Child, Preschool
  • Consanguinity
  • Female
  • Homozygote*
  • Humans
  • Infant
  • Inositol 1,4,5-Trisphosphate Receptors / genetics*
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology*
  • Male
  • Mutation*
  • Pedigree
  • Siblings


  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors

Supplementary concepts

  • Aniridia cerebellar ataxia mental deficiency