ITPR1: The missing gene in miosis-ataxia syndrome?

The association of early-onset non-progressive ataxia and miosis is an extremely rare phenotypic entity occasionally reported in the literature. To date, only one family (two siblings and their mother) has benefited from a genetic diagnosis by the identification of a missense heterozygous variant (p.Arg36Cys) in the ITPR1 gene. This gene encodes the inositol 1,4,5-trisphosphate receptor type 1, an intracellular channel that mediates calcium release from the endoplasmic reticulum. Deleterious variants in this gene are known to be associated with two types of spinocerebellar ataxia, SCA15 and SCA29, and with Gillespie syndrome that is associated with ataxia, partial iris hypoplasia, and intellectual disability. In this work, we describe a novel individual carrying a heterozygous missense variant (p.Arg36Pro) at the same position in the N-terminal suppressor domain of ITPR1 as the family previously reported, with the same phenotype associating early-onset non-progressive ataxia and miosis. This second report confirms the implication of ITPR1 in the miosis-ataxia syndrome and therefore broadens the clinical spectrum of the gene. Moreover, the high specificity of the phenotype makes it a recognizable syndrome of genetic origin.

Case report of Gillespie syndrome / 中华实用儿科临床杂志

Clinical data of a child diagnosed as Gillespie syndrome in the Department of Rehabilitation, Children′s Hospital of Nanjing Medical University in November 2019 were retrospectively analyzed.The 6-month-old boy presented psychomotor retardation, muscular hypotonia, photophobia, nystagmus and inability to focus and follow objects.Slit lamp examination of eyes revealed fixed dilation pupils, bilateral partial aniridia and characteristic iris strands.Genome sequencing and bioinformatics analysis showed a heterozygous splicing mutation in intron 26 of ITPR1 gene, c.3256-1G>A, which was a newly identified pathogenic mutation that was not been reported yet.Moreover, pa-rents of this case did not carry this mutation.It is suggested that Gillespie syndrome should be considered in children with bilateral partial aniridia, psychomotor retardation and muscular hypotonia.Genetic sequencing is helpful for early diagnosis.

Gillespie Syndrome with Partial Aniridia, Cerebellar Ataxia, Delayed Development: A case report

In 1965 Gillespie reported a new syndrome of bilateral aniridia, cerebellar ataxia, and oligophrenia (mental retardation). This new syndrome was named Gillespie syndrome. Since then only 17 cases of Gillespie syndrome have been reported in UK, Brazil, Ireland, Belgium, Australia, and US. A case of Gillespie syndrome was not reported in Korea. A 4 year-old girl has triad of Gillespie syndrome, which are partial aniridia, cerebellar ataxia and mental retardation. We confirmed this with ophthalmologic examination, brain MRI, and developmental delay. We report the typical manifestation of Gillespie syndrome in a 4 year-old girl with the brief review of literature.