{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:41:30Z","timestamp":1760150490399,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T00:00:00Z","timestamp":1702080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education\u2019s Basic Science Research Program","award":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"],"award-info":[{"award-number":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"]}]},{"name":"National Research Foundation of Korea","award":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"],"award-info":[{"award-number":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"]}]},{"name":"Gachon University Research Fund of 2019","award":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"],"award-info":[{"award-number":["NRF-2021R1A6A1A03038996","NRF-2020R1A2B5B01002463","GCU-2019-0815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Autosomal recessive spastic ataxia in Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder caused by mutations in the sacsin molecular chaperone protein (SACS) gene. Since the first report from Quebec in 1978, many pathogenic ARSACS variants with significantly reduced chaperone activities have been reported worldwide in adolescents, with presumably altered protein folding. In this study, a novel SACS mutation (p.Val1335IIe, Heterozygous) was identified in a Korean patient in their 50s with late-onset ARSACS characterized by cerebellar ataxia and spasticity without peripheral neuropathy. The mutation was confirmed via whole exome sequencing and Sanger sequencing and was predicted to likely cause disease using prediction software. RT-PCR and ELISA showed decreased SACS mRNA expression and sacsin protein concentrations in the proband, supporting its implications in diseases with pathogenicity and reduced chaperone function from haploinsufficiency. Our results revealed the pathogenicity of the SACS Val1335IIe mutation in the proband patient\u2019s disease manifestation, even though the symptoms had a limited correlation with the typical ARSACS clinical triad, which could be due to the reduced chaperon function from haploinsufficiency. Furthermore, our study suggests that variants of SACS heterozygosity may have diverse symptoms, with a wide range of disease onsets for late-onset sacsinopathy.<\/jats:p>","DOI":"10.3390\/cimb45120619","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T14:12:51Z","timestamp":1702303971000},"page":"9917-9925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Mutation in Sacsin, p.Val1335IIe, May Cause Late-Onset Sacsinopathy Due to Haploinsufficiency"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-5207","authenticated-orcid":false,"given":"Danyeong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nayoung","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Eunpyeong St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03083, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0487-8668","authenticated-orcid":false,"given":"Eva","family":"Bagyinszky","sequence":"additional","affiliation":[{"name":"Graduate School of Industrial and Environmental Engineering, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-6183","authenticated-orcid":false,"given":"Seong Soo Alexander","family":"An","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam 13120, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-5704","authenticated-orcid":false,"given":"SangYun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1017\/S0317167100024793","article-title":"Autosomal recessive spastic ataxia of Charlevoix-Saguenay","volume":"5","author":"Bouchard","year":"1978","journal-title":"Can. 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