biostudies-literatureTolonen JPHenry Smith CharitySigrid Juséliuksen SäätiöStiftelsen Alma och K. A. Snellman SäätiöMedical Research CouncilAtaxia UKUniversity of OxfordLastentautien TutkimussäätiöWellcome TrustOrionin TutkimussäätiöH2020 Excellent ScienceParkinson's UK141-151https://www.ebi.ac.uk/biostudies/studies/S-EPMC10952845biostudies-literatureUnknown39(1)<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>Cases were identified using next-generation sequencing through the Deciphering DeMovement disorders : official journal of the Movement Disorder SocietyDetailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.PMC10952845101023312223521/Z/21/ZGN2063331436356676MR/V007068/1J-1403Moore APWilliams JUusimaa JStewart HJones WDShears DShanks MEGenomics England Research ConsortiumLerman-Sagie THoulden HJarvis JHadjivassiliou MNemeth AHLynch SAHarrison REZnaczko AMartinez Albaladejo IMcGowan SParolin Schnekenberg RGranath KShaw-Smith CKneen RMcCann ETofaris GKTolonen JPDabir TEllard SBlumkin LJones GBecker EBERaskin SConti HMcEntagart MKingston HBertoli MClouston PJohnson DSims DDixit AJoss SSarkar ASuri MCeravolo GMetcalfe KMorrison PJPonger PElmslie FRankin JBlakes AJMfalseDetailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>Cases were identified using next-generation sequencing through the Deciphering De2024-01-01T00:00:00Z2024 Jan2026-07-15T09:24:29.685Z2024-11-20T19:04:45.83ZS-EPMC109528453796442610.1002/mds.29651