Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.

ABSTRACT:

Background

The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP₃ ) receptor type 1 (IP₃ R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood.

Objectives

We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy.

Methods

Cases were identified using next-generation sequencing through the Deciphering De

SUBMITTER: Tolonen JP 

PROVIDER: S-EPMC10952845 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature