Journal article

Authors list: Reis, Marlen Colleen; Härtel, Frauke; Richter, Antje Maria; Weiß, Michaela; Mösle, Lea-Theresa; Dammann, Reinhard Heinrich; Nolte, Dagmar

Publication year: 2024

Journal: International Journal of Molecular Sciences

Volume number: 25

Issue number: 22

ISSN: 1661-6596

eISSN: 1422-0067

Open access status: Gold

DOI Link: https://doi.org/10.3390/ijms252212444

Publisher: MDPI

Abstract: 
Pathogenic variants in KCNC3, which encodes the voltage-gated potassium channel Kv3.3, are associated with spinocerebellar ataxia type 13. SCA13 is a neurodegenerative disease characterized by ataxia, dysarthria and oculomotor dysfunction, often in combination with other signs and symptoms such as cognitive impairment. Known disease-causing variants are localized in the protein coding regions and predominantly in the transmembrane and voltage sensing domains. In a patient with an ataxic movement disorder and progressive cognitive decline, the c.-6C>A variant was detected in the Kozak sequence of KCNC3. The Kozak sequence is responsible for efficient initiation of translation. Functional analysis of the new c.-6C>A variant and the upstream 5'-UTR region of KCNC3 by luciferase assays, quantitative PCR and methylation analysis shows increased protein expression but no effect on transcription rate. Therefore, increased translation initiation of KCNC3 transcripts compared to wild-type Kozak sequence seems to be the cause of the increased expression. Variants in the regulatory elements of disease-causing genes probably play an underestimated role.

Harvard Citation style: Reis, M., Härtel, F., Richter, A., Weiß, M., Mösle, L., Dammann, R., et al. (2024) Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence of KCNC3, International Journal of Molecular Sciences, 25(22), Article 12444. https://doi.org/10.3390/ijms252212444

APA Citation style: Reis, M., Härtel, F., Richter, A., Weiß, M., Mösle, L., Dammann, R., & Nolte, D. (2024). Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence of KCNC3. International Journal of Molecular Sciences. 25(22), Article 12444. https://doi.org/10.3390/ijms252212444