The first case report of spinocerebellar ataxia type-40 in India: novel phenotypic and radiological (bilateral olivary degeneration) features and a comprehensive review of this remarkable radiological sign

Ghosh, Ritwik; León-Ruiz, Moisés; Dubey, Souvik; Benito‐León, Julián

doi:10.1007/s10072-022-06095-8

Cited by 4 publications

(5 citation statements)

References 54 publications

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“…Similar neurological abnormalities were described in a Chinese family, although with more severe signs, which is supported by the difference in the SARA scores as well (Supplementary Table S1) [3]. Except mild spasticity in the ankles, no other upper motor neuron symptoms or movement disorders were noticed in the patient described in this case, although these neurological alterations were frequently observed in other cases [5][6][7][8][9][10]. Brain MRI examination showed mild cerebellar and frontal lobe atrophy, but no brainstem shrinkage, bilateral olivary degeneration or any other specific structural alterations were found.…”

Section: Discussionsupporting

confidence: 83%

“…The first report by Tsoi and colleagues described a CCDC88C missense mutation in an autosomal-dominant form of SCA40 [2]. Subsequently, similar results have been reported for additional missense mutations of the gene [5][6][7][8][9][10] (Supplementary Table S3). Interestingly, the CCDC88C mutation has also been found in 2010 to cause a complex hydrocephalic brain malformation in a large family [4].…”

Section: Discussionmentioning

confidence: 54%

“…Yahia et al published a case study on a Sudanese patient with childhood-onset spastic paraparesis without cerebellar signs caused by another missense mutation of the CCDC88C gene [6]. An additional seven SCA40 patients of Kurdish, Chinese and Indian ancestry with dominantly cerebellar signs and variable movement disorders have been reported [7][8][9][10]. Segregation analysis clearly proved the putative disease-causing effect of the identified variants in four cases (p.R464H, p.D43N, p.E665K and p.R197Q).…”

Section: Introductionmentioning

confidence: 99%

“…Segregation analysis clearly proved the putative disease-causing effect of the identified variants in four cases (p.R464H, p.D43N, p.E665K and p.R197Q). This analysis was not performed in two families (p.S1974R and p.F1024L), and analysis results were controversial in one case (p.R629Q) [3,[5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene

Boros

Szpisjak

Bozó

et al. 2023

IJMS

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Spinocerebellar ataxia (SCA) 40 is an extremely rare subtype of the phenotypically and genetically diverse autosomal dominant ataxias caused by mutations of the CCDC88C gene. Most reported cases of SCA40 are characterized by late-onset cerebellar ataxia and variable extrapyramidal features; however, there is a report of a patient with early-onset spastic paraparesis as well. Here, we describe a novel missense CCDC88C mutation (p.R203W) in the hook domain of the DAPLE protein encoded by the CCDC88C gene that was identified in a female patient who developed late-onset ataxia, dysmetria and intention tremor. To explore the molecular consequences of the newly identified and previously described CCDC88C mutations, we carried out in vitro functional tests. The CCDC88C alleles were expressed in HEK293 cells, and the impact of the mutant DAPLE protein variants on JNK pathway activation and apoptosis was assessed. Our results revealed only a small-scale activation of the JNK pathway by mutant DAPLE proteins; however, increased JNK1 phosphorylation could not be detected. Additionally, none of the examined mutations triggered proapoptotic effect. In conclusion, we identified a novel mutation of the CCDC88C gene from a patient with spinocerebellar ataxia. Our results are not in accord with previous observations and do not support the primary role of the CCDC88C mutations in induction of JNK pathway activation in ataxia. Therefore, we propose that CCDC88C mutations may exert their effects through different and possibly in much broader, yet unexplored, biological processes.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene

Boros

Szpisjak

Bozó

et al. 2023

IJMS

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“…CCDC88C variations were also found in seven cases (15 individuals) with autosomal dominant spinocerebellar ataxia. These were all monoallelic and missense variants 13–19 …”

Section: Resultsmentioning

confidence: 99%

CCDC88C variants are associated with focal epilepsy and genotype–phenotype correlation

Chen,

Wang,

Zou

et al. 2024

Clinical Genetics

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CCDC88C gene, which encodes coiled‐coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole‐exome sequencing (trio‐based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult‐onset epilepsy, whereas patients with biallelic variants displayed infant‐onset epilepsy. They all responded well to anti‐seizure medications and were seizure‐free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non‐classical splicing and a variant located at crucial domain, suggesting a sub‐molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy‐associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus‐associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

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Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs

Leong

Pal

Cai

et al. 2023

Journal of Controlled Release

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The first case report of spinocerebellar ataxia type-40 in India: novel phenotypic and radiological (bilateral olivary degeneration) features and a comprehensive review of this remarkable radiological sign

Cited by 4 publications

References 54 publications

Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene

Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene

CCDC88C variants are associated with focal epilepsy and genotype–phenotype correlation

Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs

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