ITPR1: The missing gene in miosis–ataxia syndrome?

Abstract

AbstractThe 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.