Insights into heterozygous ITPR1 variants associated with ataxia and miosis
Wincent, J.; Zhang, S.; Nolan, A.; Nordin, F.; Kvarnung, M.; Uhlen, P.; Paucar, M.; Eidhof, I.
Show abstract
BackgroundOnly twice have variants in the ITPR1 gene been described among patients with ataxia and miosis. Functional characterization of these variants is lacking. ObjectiveTo 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. MethodsClinical 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. ResultsAtaxia 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. ConclusionsHere, 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.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling 91%
- Proteomic and structural comparison between cilia from primary ciliary dyskinesia patients with a DNAH5 defect 90%
- FAIM opposes stress-induced loss of viability and blocks the formation of protein aggregates 90%
Similar papers in this journal
- Mutations affecting the N-terminal domains of SHANK3 point to different pathomechanisms in neurodevelopmental disorders. 94%
- A new perspective on the evolution of the interaction between the Vg/VGLL1-3 proteins and the TEAD transcription factors 92%
- Cyclase-associated protein 2 (CAP2) controls MRTF-A localization and SRF activity in mouse embryonic fibroblasts 92%
Similar papers in this journal
Similar papers in this journal
- Impaired SorLA maturation and trafficking as a new mechanism for SORL1 missense variants in Alzheimer disease 93%
- Neuropathology of RAN translation proteins in Fragile X-associated Tremor/Ataxia Syndrome 92%
- Organotypic slice culture model demonstrates interneuronal spreading of alpha-synuclein aggregates 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.