Two Novel CACNA1A Gene Mutations Associated With Episodic Ataxia Type 2 and Interictal Dystonia

Striatal cell-type–specific molecular signatures reveal therapeutic targets in a model of dystonia

“…88,89 Subsequently, pathogenic variants in multiple genes involved in calcium homeostasis were identified in individuals with dystonia, including ANO3, CACNA1A, CACNA1B, CAMK4, CAMTA1, HPCA, KCNMA1, and KCTD17. 4,[90][91][92][93][94][95][96][97] Our results suggest that glutamatergic neurotransmission is enhanced in dSPNs but diminished in iSPNs in DRD mice, a premise suggested by gene expression data and supported by electrophysiologic experiments. Ensembles of dSPNs and iSPNs receive spatially and temporally organized glutamatergic afferents from the cortex.…”

Striatal cell-type–specific molecular signatures reveal therapeutic targets in a model of dystonia

“…88,89 Subsequently, pathogenic variants in multiple genes involved in calcium homeostasis were identified in individuals with dystonia, including ANO3, CACNA1A, CACNA1B, CAMK4, CAMTA1, HPCA, KCNMA1, and KCTD17. 4,[90][91][92][93][94][95][96][97] Our results suggest that glutamatergic neurotransmission is enhanced in dSPNs but diminished in iSPNs in DRD mice, a premise suggested by gene expression data and supported by electrophysiologic experiments. Ensembles of dSPNs and iSPNs receive spatially and temporally organized glutamatergic afferents from the cortex.…”

Case report of novel CACNA1A gene mutation causing episodic ataxia type 2

“…Both acetazolamide and 4-aminopyridine reduce the frequency of attacks, 1 and our patient has noted significant improvement on low-dose acetazolamide. It is difficult to interpret our patient’s symptomatic improvement following initiation of steroids and decline upon steroid withdrawal.…”

Investigating ITM2B‐associated ataxia in a Taiwanese cerebellar ataxia cohort

“…Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38 , 39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40 , 41 , 42 as well as some rare autosomal recessive cerebellar ataxias. 43 , 44 MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients. However, due to the rarity of the cases, further studies are necessary to confirm whether this is a universal feature of ITM2B ‐associated ataxias.…”

“…These findings, along with the clinical profiles of our cases and a previously reported Chinese proband, 12 suggest early involvement of the spinocerebellum and vestibulocerebellum. Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38,39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40–42 as well as some rare autosomal recessive cerebellar ataxias 43,44 . MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients.…”

Striatal cell-type–specific molecular signatures reveal therapeutic targets in a model of dystonia

“…88,89 Subsequently, pathogenic variants in multiple genes involved in calcium homeostasis were identified in individuals with dystonia, including ANO3, CACNA1A, CACNA1B, CAMK4, CAMTA1, HPCA, KCNMA1, and KCTD17. 4,[90][91][92][93][94][95][96][97] Our results suggest that glutamatergic neurotransmission is enhanced in dSPNs but diminished in iSPNs in DRD mice, a premise suggested by gene expression data and supported by electrophysiologic experiments. Ensembles of dSPNs and iSPNs receive spatially and temporally organized glutamatergic afferents from the cortex.…”

Case report of novel CACNA1A gene mutation causing episodic ataxia type 2

“…Both acetazolamide and 4-aminopyridine reduce the frequency of attacks, 1 and our patient has noted significant improvement on low-dose acetazolamide. It is difficult to interpret our patient’s symptomatic improvement following initiation of steroids and decline upon steroid withdrawal.…”

Investigating ITM2B‐associated ataxia in a Taiwanese cerebellar ataxia cohort

“…Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38 , 39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40 , 41 , 42 as well as some rare autosomal recessive cerebellar ataxias. 43 , 44 MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients. However, due to the rarity of the cases, further studies are necessary to confirm whether this is a universal feature of ITM2B ‐associated ataxias.…”

“…These findings, along with the clinical profiles of our cases and a previously reported Chinese proband, 12 suggest early involvement of the spinocerebellum and vestibulocerebellum. Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38,39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40–42 as well as some rare autosomal recessive cerebellar ataxias 43,44 . MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients.…”

Striatal cell-type–specific molecular signatures reveal therapeutic targets in a model of dystonia

“…88,89 Subsequently, pathogenic variants in multiple genes involved in calcium homeostasis were identified in individuals with dystonia, including ANO3, CACNA1A, CACNA1B, CAMK4, CAMTA1, HPCA, KCNMA1, and KCTD17. 4,[90][91][92][93][94][95][96][97] Our results suggest that glutamatergic neurotransmission is enhanced in dSPNs but diminished in iSPNs in DRD mice, a premise suggested by gene expression data and supported by electrophysiologic experiments. Ensembles of dSPNs and iSPNs receive spatially and temporally organized glutamatergic afferents from the cortex.…”

Case report of novel CACNA1A gene mutation causing episodic ataxia type 2

“…Both acetazolamide and 4-aminopyridine reduce the frequency of attacks, 1 and our patient has noted significant improvement on low-dose acetazolamide. It is difficult to interpret our patient’s symptomatic improvement following initiation of steroids and decline upon steroid withdrawal.…”

Investigating ITM2B‐associated ataxia in a Taiwanese cerebellar ataxia cohort

“…Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38 , 39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40 , 41 , 42 as well as some rare autosomal recessive cerebellar ataxias. 43 , 44 MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients. However, due to the rarity of the cases, further studies are necessary to confirm whether this is a universal feature of ITM2B ‐associated ataxias.…”

“…These findings, along with the clinical profiles of our cases and a previously reported Chinese proband, 12 suggest early involvement of the spinocerebellum and vestibulocerebellum. Unlike degenerative cerebellar ataxias like SCA and MSA that are typically influencing the entire cerebellum, 38,39 predominant vermis involvement is more common in acquired ataxias such as immune‐mediated cerebellar ataxias and alcoholic cerebellar degeneration, 40–42 as well as some rare autosomal recessive cerebellar ataxias 43,44 . MRS data of ITM2B ‐associated ataxia has never been investigated before, and our study is the first to show earlier dysfunction of cerebellar vermis compared to the hemispheres in affected patients.…”