Insights into heterozygous ITPR1 variants associated with ataxia and miosis
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Only twice have variants in the ITPR1 gene been described among patients with ataxia and miosis. Functional characterization of these variants is lacking.
Objective
To characterize a family affected by congenital ataxia and miosis associated with a novel ITPR1 variant and to provide a functional assessment for it and two previously reported variants.
Methods
Clinical characterization, genetic investigations, and segregation were performed. A novel variant c.7697T>C in ITPR1 was identified, HEK cells were transfected with vectors carrying our variant and two other previously published variants associated with ataxia and miosis.
Results
Ataxia was non-progressive in the reported family, the c.7697T>c ITPR1 variant segregated with disease. Functional validation showed that all the three ITPR1 variants were associated with reduced intracellular calcium release.
Conclusions
Here, we present for the first time evidence of pathogenicity for 3 heterozygous ITPR1 variants in association with ataxia and miosis. Despite being localized in different ITPR1 protein domains, these variants converged on common functional defects.
