relation: http://publicatio.bibl.u-szeged.hu/26844/
title: Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene
creator:  Boros Fanni Annamária
creator:  Szpisjak László
creator:  Bozó Renáta
creator:  Kelemen Evelyn
creator:  Zádori Dénes
creator:  Salamon András
creator:  Danis Judit
creator:  Kalmár Tibor
creator:  Maróti Zoltán
creator:  Molnár Mária Judit
creator:  Klivényi Péter
creator:  Széll Márta
creator:  Ádám Éva
subject: 03.02. Klinikai orvostan
description: 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.
date: 2023
type: Folyóiratcikk
type: PeerReviewed
format: text
identifier: http://publicatio.bibl.u-szeged.hu/26844/1/ijms-24-02617.pdf
identifier:     Boros Fanni Annamária;  Szpisjak László;  Bozó Renáta;  Kelemen Evelyn;  Zádori Dénes;  Salamon András;  Danis Judit;  Kalmár Tibor;  Maróti Zoltán;  Molnár Mária Judit;  Klivényi Péter;  Széll Márta;  Ádám Éva: Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (3).   ISSN 1661-6596 (2023)     
identifier: doi:10.3390/ijms24032617
relation: https://doi.org/10.3390/ijms24032617
relation: 33606248
language: eng