TY  - JOUR
ID  - publicatio26844
A1  -  Boros Fanni Annamária
A1  -  Szpisjak László
A1  -  Bozó Renáta
A1  -  Kelemen Evelyn
A1  -  Zádori Dénes
A1  -  Salamon András
A1  -  Danis Judit
A1  -  Kalmár Tibor
A1  -  Maróti Zoltán
A1  -  Molnár Mária Judit
A1  -  Klivényi Péter
A1  -  Széll Márta
A1  -  Ádám Éva
N2  - 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.
UR  - https://doi.org/10.3390/ijms24032617
EP  - 11
TI  - Spinocerebellar Ataxia in a Hungarian Female Patient with a Novel Variant of Unknown Significance in the CCDC88C Gene
SN  - 1661-6596
Y1  - 2023///
VL  - 24
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
AV  - public
IS  - 3
ER  -