Superior Cerebellar Atrophy: An Imaging Clue to Diagnose ITPR1-Related Disorders
Authors:
- Romina RomanielloRomina Romaniello
- Ludovica PascaLPLudovica Pasca
- Elena PanzeriEPElena Panzeri
- Fulvio D’abruscoFDFulvio D’abrusco
- Lorena TravagliniLTLorena Travaglini
- Valentina SerpieriVSValentina Serpieri
- Sabrina SignoriniSSSabrina Signorini
- Chiara AielloCAChiara Aiello
- Enrico BertiniEBEnrico Bertini
- Maria Teresa BassiMBMaria Teresa Bassi
- Enza Maria ValenteEVEnza Maria Valente
- Ginevra ZanniGZGinevra Zanni
Open Access
- 16 June 2022
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 23 (12) , 6723
Abstract
The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene encodes an InsP3-gated calcium channel that modulates intracellular Ca2+ release and is particularly expressed in cerebellar Purkinje cells. Pathogenic variants in the ITPR1 gene are associated with different types of autosomal dominant spinocerebellar ataxia: SCA15 (adult onset), SCA29 (early-onset), and Gillespie syndrome. Cerebellar atrophy/hypoplasia is invariably detected, but a recognizable neuroradiological pattern has not been identified yet. With the aim of describing ITPR1-related neuroimaging findings, the brain MRI of 14 patients with ITPR1 variants (11 SCA29, 1 SCA15, and 2 Gillespie) were reviewed by expert neuroradiologists. To further evaluate the role of superior vermian and hemispheric cerebellar atrophy as a clue for the diagnosis of ITPR1-related conditions, the ITPR1 gene was sequenced in 5 patients with similar MRI pattern, detecting pathogenic variants in 4 of them. Considering the whole cohort, a distinctive neuroradiological pattern consisting in superior vermian and hemispheric cerebellar atrophy was identified in 83% patients with causative ITPR1 variants, suggesting this MRI finding could represent a hallmark for ITPR1-related disorders.Keywords
Funding Information
- Italian Ministry of Health (# RC2021 265, RC2022, RF-2019-266 12369368, 5X MILLE, 268 # Care4NeuroRare, No 739510)
- Ricerca Finalizzata (# RC2021 265, RC2022, RF-2019-266 12369368, 5X MILLE, 268 # Care4NeuroRare, No 739510)
- Fondazione Mariani (# RC2021 265, RC2022, RF-2019-266 12369368, 5X MILLE, 268 # Care4NeuroRare, No 739510)
- Fondazione Regionale Lombarda per la Ricerca Biomedica FRRB (# RC2021 265, RC2022, RF-2019-266 12369368, 5X MILLE, 268 # Care4NeuroRare, No 739510)
- European Reference Network for Rare 269 Neurological Diseases—Project (# RC2021 265, RC2022, RF-2019-266 12369368, 5X MILLE, 268 # Care4NeuroRare, No 739510)
This publication has 25 references indexed in Scilit:
- ITPR1 gene p.Val1553Met mutation in Russian family with mild Spinocerebellar ataxiaCerebellum & Ataxias, 2016
- Differential Diagnosis of Cerebellar Atrophy in Childhood: An UpdateNeuropediatrics, 2015
- Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 geneJournal of Neurology, 2015
- Diagnostic utility of whole exome sequencing in patients showing cerebellar and/or vermis atrophy in childhoodneurogenetics, 2013
- Type 1 Inositol Trisphosphate Receptor Regulates Cerebellar Circuits by Maintaining the Spine Morphology of Purkinje Cells in Adult MiceJournal of Neuroscience, 2013
- Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxiaOrphanet Journal of Rare Diseases, 2012
- An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: A genetic, clinical and radiological descriptionMovement Disorders, 2010
- Two Italian Families with ITPR1 Gene Deletion Presenting a Broader Phenotype of SCA15The Cerebellum, 2010
- Total deletion and a missense mutation of ITPR1 in Japanese SCA15 familiesNeurology, 2008
- Differential diagnosis of cerebellar atrophy in childhoodEuropean Journal of Paediatric Neurology, 2008