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Advanced Neurology Neurologic manifestation associated with an RYR2 variant

reticulum Ca leaks may activate Ca -dependent signaling Elizabeth’s Medical Center. Written informed consent to
2+
2+
pathways involved in Alzheimer’s disease pathogenesis. participate in the study was obtained from the patients and
20
Although the father has not been diagnosed with their guardians.
Alzheimer’s disease, his memory dysfunction may reflect
these underlying mechanisms. In addition, RYR2 mutations Consent for publication
have been implicated in neurocardiac channelopathies, Written informed consent for publication of their details
which may explain the autonomic dysfunction observed in was obtained from the patients and their guardians.
this case. This case report underscores the need for further
research to clarify this suggested association. Availability of data
4. Conclusion All data generated or analyzed during the study are
included in the article. Further enquiries can be directed to
RYR2 variants have been extensively studied in the context the corresponding author.
of CPVT and AVRD2. Emerging evidence suggests that
these variants also impact other organ systems, including the References
brain. In this case report, both the father and son presented 1. Lanner JT, Georgiou DK, Joshi AD and Hamilton SL.
with neurological symptoms linked to an RYR2 mutation Ryanodine receptors: Structure, expression, molecular
(p.Asn2517Ser). The father exhibited cognitive dysfunction, details, and function in calcium release. Cold Spring Harb
consistent with previous studies implicating RYR2 variants in Perspect Biol. 2010;2(11):a003996.
the development of Alzheimer’s-like disease. In contrast, the doi: 10.1101/cshperspect.a003996
son displayed symptoms of autonomic dysfunction that could
not be attributed to known causes, such as mitochondrial 2. Eisner DA, Caldwell JL, Kistamás K, Trafford AW. Calcium
disease, vitamin deficiencies, or structural abnormalities. Given and excitation-contraction coupling in the heart. Circ Res.
the shared RYR2 variant and the established role of RyR2 in the 2017;121(2):181-195.
brain, this case highlights the potential for RYR2 mutations to doi: 10.1161/CIRCRESAHA.117.310230
manifest in diverse neurological phenotypes. Future studies 3. Liu C, Zhang A, Yan N, Song C. Atomistic details of charge/
are needed to identify and characterize additional patients space competition in the Ca2+ selectivity of ryanodine
with this RYR2 mutation to further elucidate its phenotypic receptors. J Phys Chem Lett. 2021;12(17):4286-4291.
spectrum and underlying mechanisms.
doi: 10.1021/acs.jpclett.1c00681
Acknowledgments 4. Takeshima H, Nishimura S, Matsumoto T, et al.
Primary structure and expression from complementary
None. DNA of skeletal muscle ryanodine receptor. Nature.
1989;339(6224):439-445.
Funding
doi: 10.1038/339439a0
None.
5. Furuichi T, Furutama D, Hakamata Y, Nakai J, Takeshima H,
Conflict of interest Mikoshiba K. Multiple types of ryanodine receptor/Ca2+
release channels are differentially expressed in rabbit brain.
The authors declare that they have no competing interests. J Neurosci. 1994;14(8):4794-4805.

Author contributions doi: 10.1523/JNEUROSCI.14-08-04794.1994
6. Tiso N, Stephan DA, Nava A, et al. Identification of mutations
Conceptualization: Anna Hohler, Okeanis Vaou in the cardiac ryanodine receptor gene in families affected
Formal analysis: Liam Power, Justin Ho, Charly Edmiston, with arrhythmogenic right ventricular cardiomyopathy
Leilani Miranda type 2 (ARVD2). Hum Mol Genet. 2001;10(3):189-194.
Investigation: Liam Power, Justin Ho, Charly Edmiston
Writing-original draft: Liam Power, Justin Ho, Charly doi: 10.1093/hmg/10.3.189
Edmiston, Leilani Miranda 7. Priori SG, Chen SR. Inherited dysfunction of sarcoplasmic
Writing-review & editing: Liam Power, Justin Ho, Charly reticulum Ca2+ handling and arrhythmogenesis. Circ Res.
Edmiston, Leilani Miranda, Anna Hohler 2011;108(7):871-883.
doi: 10.1161/CIRCRESAHA.110.226845
Ethics approval and consent to participate
8. Giannini G, Conti A, Mammarella S, Scrobogna M,
This retrospective case study was conducted with ethics Sorrentino V. The ryanodine receptor/calcium channel
approval waived by the Institutional Review Board of St. genes are widely and differentially expressed in murine brain

Volume 4 Issue 3 (2025) 120 doi: 10.36922/an.4509