{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T03:04:03Z","timestamp":1777777443471,"version":"3.51.4"},"reference-count":108,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2013Next Generation EU\u2013PNRR M6C2\u2013Investimento 2.1 Valorizzazione e Potenziamento della Ricerca Biomedica del SSN","award":["PNRR-MR1-2022-12375730"],"award-info":[{"award-number":["PNRR-MR1-2022-12375730"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cerebellar ataxias are a group of disorders characterized by clumsy movements because of defective muscle control. In affected individuals, muscular impairment might have an impact on activities like walking, balance, hand coordination, speech, and feeding, as well as eye movements. The development of symptoms typically takes place during the span of adolescence, and it has the potential to cause distress for individuals in many areas of their lives, including professional and interpersonal relationships. Although skeletal muscle is understudied in ataxias, its examination may provide hitherto unexplored details in this family of disorders. Observing muscle involvement can assist in diagnosing conditions where genetic tests alone are inconclusive. Furthermore, it helps determine the stage of progression of a pathology that might otherwise be challenging to assess. In this study, we reviewed the main scientific literature reporting on skeletal muscle examination in autosomal recessive cerebellar ataxias (ARCAs), with a focus on the rare Marinesco\u2013Sj\u00f6gren syndrome. (MSS). Our aim was to highlight the similarities in muscle alterations observed in ARCA patients while also considering data gathered from preclinical models. Analyzing the similarities among these disorders could enhance our understanding of the unidentified mechanisms underlying the phenotypic evolution of some less common conditions.<\/jats:p>","DOI":"10.3390\/ijms26146736","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6736","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Skeletal Muscle Pathology in Autosomal Recessive Cerebellar Ataxias: Insights from Marinesco\u2013Sj\u00f6gren Syndrome"],"prefix":"10.3390","volume":"26","author":[{"given":"Fabio","family":"Bellia","sequence":"first","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Federici","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9999-5823","authenticated-orcid":false,"given":"Valentina","family":"Gatta","sequence":"additional","affiliation":[{"name":"Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Functional Genetics Unit, Center of Excellence on Aging (Ce.S.I.-MeT), 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Oncology Hematology, Pescara Hospital, 65124 Pescara, Italy"},{"name":"Department of Medical, Oral and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2555-3571","authenticated-orcid":false,"given":"Michele","family":"Sallese","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S391","DOI":"10.1016\/S1353-8020(08)70036-1","article-title":"Ataxias","volume":"13","author":"Klockgether","year":"2007","journal-title":"Park. Relat. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/WCO.0b013e32832b9897","article-title":"Cerebellar ataxias","volume":"22","author":"Manto","year":"2009","journal-title":"Curr. Opin. Neurol."},{"key":"ref_3","first-page":"97","article-title":"Nouvelle maladie familiale caracterisee par une cataracte congenitale et un arret du developpement somato-neuro-psychique","volume":"26","author":"Marinesco","year":"1931","journal-title":"Encephale"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000105590","article-title":"Hereditary congenital spinocerebellar ataxia accompanied by congenital cataract and oligophrenia; a genetic and clinical investigation","volume":"10","author":"Sjogren","year":"1950","journal-title":"Confin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1212\/WNL.12.12.836","article-title":"Cerebellar ataxia, congenital cataracts, and retarded somatic and mental maturation. Report of cases of Marinesco-Sjogren syndrome","volume":"12","author":"Alter","year":"1962","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.irn.2022.06.010","article-title":"Chapter Four-Sex and gender differences in movement disorders: Parkinson\u2019s disease, essential tremor, dystonia and chorea","volume":"Volume 164","author":"Moro","year":"2022","journal-title":"International Review of Neurobiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.yfrne.2009.04.014","article-title":"Neuroprotective actions of sex steroids in Parkinson\u2019s disease","volume":"30","author":"Bourque","year":"2009","journal-title":"Front. Neuroendocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zielonka, D., and Stawinska-Witoszynska, B. (2020). Gender Differences in Non-sex Linked Disorders: Insights From Huntington\u2019s Disease. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00571"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jns.2011.05.023","article-title":"Mortality in Friedreich Ataxia","volume":"307","author":"Tsou","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ichhaporia, V.P., and Hendershot, L.M. (2021). Role of the HSP70 Co-Chaperone SIL1 in Health and Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041564"},{"key":"ref_11","first-page":"197","article-title":"Marinesco-Sjogren syndrome. 1st anatomo-clinical study","volume":"14","author":"Todorov","year":"1965","journal-title":"J. Genet. Hum."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/ana.410240416","article-title":"Myopathy with unique ultrastructural feature in Marinesco-Sj\u00f6gren syndrome","volume":"24","author":"Sewry","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/nan.12588","article-title":"Review: Protein misfolding diseases-the rare case of Marinesco-Sj\u00f6gren syndrome","volume":"46","author":"Chiesa","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_14","first-page":"289","article-title":"The ER function BiP is a master regulator of ER function","volume":"71","author":"Hendershot","year":"2004","journal-title":"Mt. Sinai. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1534-5807(02)00203-4","article-title":"ER Stress Regulation of ATF6 Localization by Dissociation of BiP\/GRP78 Binding and Unmasking of Golgi Localization Signals","volume":"3","author":"Shen","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gardner, B.M., Pincus, D., Gotthardt, K., Gallagher, C.M., and Walter, P. (2013). Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a013169"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jns.2017.12.010","article-title":"Targeting the enhanced ER stress response in Marinesco-Sj\u00f6gren syndrome","volume":"385","author":"Kashimada","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1038\/ng1677","article-title":"The gene disrupted in Marinesco-Sj\u00f6gren syndrome encodes SIL1, an HSPA5 cochaperone","volume":"37","author":"Anttonen","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1038\/ng1678","article-title":"Mutations in SIL1 cause Marinesco-Sj\u00f6gren syndrome, a cerebellar ataxia with cataract and myopathy","volume":"37","author":"Senderek","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8552","DOI":"10.1074\/jbc.M111.333286","article-title":"C-terminal mutations destabilize SIL1\/BAP and can cause Marinesco-Sj\u00f6gren syndrome","volume":"287","author":"Howes","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1093\/brain\/95.4.675","article-title":"Marinesco-Sj\u00f6gren Syndrome Report of an Autopsy","volume":"95","author":"Mahloudji","year":"1972","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109221","DOI":"10.1016\/j.isci.2024.109221","article-title":"Fat infiltration in skeletal muscle: Influential triggers and regulatory mechanism","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1136\/jmg.39.11.838","article-title":"Linkage to 18qter differentiates two clinically overlapping syndromes: Congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndrome and Marinesco-Sj\u00f6gren syndrome","volume":"39","author":"Chaigne","year":"2002","journal-title":"J. Med. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00415-005-0983-9","article-title":"Myopathy is a prominent featurein Marinesco-Sj\u00f6gren syndrome","volume":"253","author":"Mahjneh","year":"2006","journal-title":"J. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.nbd.2018.11.019","article-title":"SIL1 deficiency causes degenerative changes of peripheral nerves and neuromuscular junctions in fish, mice and human","volume":"124","author":"Phan","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00401-013-1224-4","article-title":"Myopathy in Marinesco\u2013Sj\u00f6gren syndrome links endoplasmic reticulum chaperone dysfunction to nuclear envelope pathology","volume":"127","author":"Roos","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000116305","article-title":"Myopathy in Marinesco-Sjogren syndrome","volume":"26","author":"Superneau","year":"1987","journal-title":"Eur. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s004010050727","article-title":"Apoptotic nuclear degeneration in Marinesco-Sj\u00f6gren syndrome","volume":"94","author":"Suzuki","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ejpn.2011.07.016","article-title":"The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children","volume":"16","author":"Terracciano","year":"2012","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1600-0404.1991.tb04921.x","article-title":"Myopathy in Marinesco-Sj\u00f6gren syndrome: An electrophysiological study","volume":"84","author":"Torbergsen","year":"1991","journal-title":"Acta Neurol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1212\/WNL.35.3.415","article-title":"Marinesco-Sj\u00f6gren syndrome","volume":"35","author":"Walker","year":"1985","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/0387-7604(95)00088-7","article-title":"Muscle pathology in Marinesco-Sjo\u00a8gren syndrome: A unique ultrastructural feature","volume":"18","author":"Sasaki","year":"1996","journal-title":"Brain Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/0887-8994(91)90049-Q","article-title":"Congenital muscular dystrophy in Marinesco-Sj\u00f6gren syndrome","volume":"7","author":"Tachi","year":"1991","journal-title":"Pediatr. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/0887-8994(93)90114-R","article-title":"Rapid cataract formation in Marinesco-Sj\u00f6gren syndrome","volume":"9","author":"Ishikawa","year":"1993","journal-title":"Pediatr. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0022-510X(89)90010-5","article-title":"Muscle pathology in Marinesco-Sj\u00f6gren syndrome","volume":"89","author":"Komiyama","year":"1989","journal-title":"J. Neurol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1055\/s-2008-1071368","article-title":"Neuropathy with lysosomal changes in Marinesco-Sj\u00f6gren syndrome: Fine structural findings in skeletal muscle and conjunctiva","volume":"23","author":"Zimmer","year":"1992","journal-title":"Neuropediatrics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/BF00308914","article-title":"Myopathy in Marinesco-Sj\u00f6gren syndrome: An ultrastructural study","volume":"80","author":"Goto","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1055\/s-2008-1052473","article-title":"A syndrome with juvenile cataract, cerebellar atrophy, mental retardation and myopathy","volume":"18","author":"Herva","year":"1987","journal-title":"Neuropediatrics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3634","DOI":"10.1093\/brain\/awt283","article-title":"SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome","volume":"136","author":"Krieger","year":"2013","journal-title":"Brain"},{"key":"ref_40","first-page":"97","article-title":"Marinesco Sj\u00f6gren Syndrome with Rhabdomyolysis. A New Subtype of the Disease","volume":"29","author":"Zafiriou","year":"2007","journal-title":"Neuropediatrics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cmet.2009.10.008","article-title":"Autophagy Is Required to Maintain Muscle Mass","volume":"10","author":"Masiero","year":"2009","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/ng1620","article-title":"Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP","volume":"37","author":"Zhao","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3233\/JND-160152","article-title":"Sil1-Mutant Mice Elucidate Chaperone Function in Neurological Disorders","volume":"3","author":"Buchkremer","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1093\/hmg\/ddy152","article-title":"PERK inhibition delays neurodegeneration and improves motor function in a mouse model of Marinesco-Sj\u00f6gren syndrome","volume":"27","author":"Grande","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1097\/WNR.0000000000000816","article-title":"Longitudinal analysis of motor symptoms and histopathology in woozy mice, a model of cerebellar ataxia","volume":"28","author":"Hayashi","year":"2017","journal-title":"NeuroReport"},{"key":"ref_46","first-page":"dmm.33043","article-title":"SIL1, the endoplasmic-reticulum-localized BiP co-chaperone, plays a crucial role in maintaining skeletal muscle proteostasis and physiology","volume":"11","author":"Ichhaporia","year":"2018","journal-title":"Dis. Models Mech."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kawahara, G., and Hayashi, Y.K. (2016). Characterization of Zebrafish Models of Marinesco-Sj\u00f6gren Syndrome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165563"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1093\/hmg\/10.21.2463","article-title":"The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly","volume":"10","author":"Huynen","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/jnc.12220","article-title":"Frataxin: A protein in search for a function","volume":"126","author":"Pastore","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"NS20180060","DOI":"10.1042\/NS20180060","article-title":"Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease","volume":"2","author":"Clark","year":"2018","journal-title":"Neuronal. Signal."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100266","DOI":"10.1016\/j.imu.2019.100266","article-title":"Analysis of Friedreich\u2019s ataxia patient clinical data reveals importance of accurate GAA repeat determination in disease prognosis and gender differences in cardiac measures","volume":"17","author":"Ghorbani","year":"2019","journal-title":"Inform. Med. Unlocked"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Indelicato, E., Faserl, K., Amprosi, M., Nachbauer, W., Schneider, R., Wanschitz, J., Sarg, B., and Boesch, S. (2023). Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich\u2019s ataxia. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1289027"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/hmg\/9.2.275","article-title":"Clinical, biochemical and molecular genetic correlations in Friedreich\u2019s ataxia","volume":"9","author":"Bradley","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0960-8966(00)00108-5","article-title":"Mitochondrial impairment of human muscle in Friedreich ataxia in vivo","volume":"10","author":"Vorgerd","year":"2000","journal-title":"Neuromuscul. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/NEN.0b013e31825fed76","article-title":"Skeletal Muscle Involvement in Friedreich Ataxia and Potential Effects of Recombinant Human Erythropoietin Administration on Muscle Regeneration and Neovascularization","volume":"71","author":"Nachbauer","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nachbauer, W., Boesch, S., Schneider, R., Eigentler, A., Wanschitz, J., Poewe, W., and Schocke, M. (2013). Bioenergetics of the Calf Muscle in Friedreich Ataxia Patients Measured by 31P-MRS Before and After Treatment with Recombinant Human Erythropoietin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069229"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ng1927","article-title":"Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia","volume":"39","author":"Dion","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/cm.21182","article-title":"Nesprin-1 and nesprin-2 regulate endothelial cell shape and migration","volume":"71","author":"King","year":"2014","journal-title":"Cytoskeleton"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/ejhg.2016.144","article-title":"Homozygous SYNE1 mutation causes congenital onset of muscular weakness with distal arthrogryposis: A genotype\u2013phenotype correlation","volume":"25","author":"Baumann","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Serag, M., Plutino, M., Charles, P., Azulay, J.-P., Chaussenot, A., Paquis-Flucklinger, V., Ait-El-Mkadem Saadi, S., and Rouzier, C. (2023). A Case Report of SYNE1 Deficiency-Mimicking Mitochondrial Disease and the Value of Pangenomic Investigations. Genes, 14.","DOI":"10.3390\/genes14122154"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1212\/01.WNL.0000055089.39373.FC","article-title":"Cerebellar ataxia and coenzyme Q10 deficiency","volume":"60","author":"Lamperti","year":"2003","journal-title":"Neurology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40673-015-0035-x","article-title":"Mitochondrial pathology in progressive cerebellar ataxia","volume":"2","author":"Bargiela","year":"2015","journal-title":"Cerebellum Ataxias"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.nmd.2021.05.014","article-title":"A novel MT-CO2 variant causing cerebellar ataxia and neuropathy: The role of muscle biopsy in diagnosis and defining pathogenicity","volume":"31","author":"Baty","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zierz, C.M., Baty, K., Blakely, E.L., Hopton, S., Falkous, G., Schaefer, A.M., Hadjivassiliou, M., Sarrigiannis, P.G., Ng, Y.S., and Taylor, R.W. (2019). A Novel Pathogenic Variant in MT-CO2 Causes an Isolated Mitochondrial Complex IV Deficiency and Late-Onset Cerebellar Ataxia. J. Clin. Med., 8.","DOI":"10.3390\/jcm8060789"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40673-020-00122-0","article-title":"Should we investigate mitochondrial disorders in progressive adult-onset undetermined ataxias?","volume":"7","author":"Pedroso","year":"2020","journal-title":"Cerebellum Ataxias"},{"key":"ref_66","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993\u20132025). Spastic Paraplegia 7. GeneReviews\u00ae, University of Washington."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1212\/WNL.56.4.467","article-title":"Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England","volume":"56","author":"McDermott","year":"2001","journal-title":"Neurology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1093\/brain\/aws224","article-title":"Genotype-phenotype correlations in spastic paraplegia type 7: A study in a large Dutch cohort","volume":"135","author":"Kremer","year":"2012","journal-title":"Brain"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)81203-9","article-title":"Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease","volume":"93","author":"Casari","year":"1998","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/humu.20682","article-title":"A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia","volume":"29","author":"Arnoldi","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wedding, I.M., Koht, J., Tran, G.T., Misceo, D., Selmer, K.K., Holmgren, A., Frengen, E., Bindoff, L., Tallaksen, C.M.E., and Tzoulis, C. (2014). Spastic Paraplegia Type 7 Is Associated with Multiple Mitochondrial DNA Deletions. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086340"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/brain\/awh125","article-title":"A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia","volume":"127","author":"Wilkinson","year":"2004","journal-title":"Brain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E44","DOI":"10.1002\/mus.26882","article-title":"A novel phenotype of hereditary spastic paraplegia type 7 associated with a compound heterozygous mutation in paraplegin","volume":"62","author":"Mahoney","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","article-title":"Ataxia telangiectasia: A review","volume":"11","author":"Wright","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1111\/ene.16028","article-title":"Peripheral polyneuropathy in children and young adults with ataxia\u2013telangiectasia","volume":"30","author":"Theis","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s13023-015-0373-z","article-title":"Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: A cohort study","volume":"10","author":"Pommerening","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1055\/s-2007-985899","article-title":"Neuromuscular abnormalities in ataxia telangiectasia: A clinical, electrophysiological and muscle ultrasound study","volume":"38","author":"Verhagen","year":"2007","journal-title":"Neuropediatrics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/ppul.20209","article-title":"Interstitial lung disease in patients with ataxia-telangiectasia","volume":"39","author":"Schroeder","year":"2005","journal-title":"Pediatr. Pulmonol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/ppul.22828","article-title":"Effects of inspiratory muscle training on lung volumes, respiratory muscle strength, and quality of life in patients with ataxia telangiectasia","volume":"49","author":"Gimenes","year":"2014","journal-title":"Pediatr. Pulmonol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/jhg.2009.104","article-title":"A novel nonsense mutation in a Japanese family with ataxia with oculomotor apraxia type 2 (AOA2)","volume":"54","author":"Nakamura","year":"2009","journal-title":"J. Hum. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/j.1469-8749.2006.tb01308.x","article-title":"Atypical presentation of ataxia-oculomotor apraxia type 1","volume":"48","author":"Shah","year":"2006","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1001\/archneur.65.7.958","article-title":"Clinical and Molecular Findings of Ataxia With Oculomotor Apraxia Type 2 in 4 Families","volume":"65","author":"Anheim","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1055\/s-2005-865610","article-title":"Mitochondrial Dysfunction in a Patient with Joubert Syndrome","volume":"36","author":"Morava","year":"2005","journal-title":"Neuropediatrics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/BF02337167","article-title":"Congenital muscular dystrophy and cerebellar vermis agenesis in two brothers","volume":"9","author":"Arancio","year":"1988","journal-title":"Ital. J. Neuro. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"374","DOI":"10.5334\/tohm.298","article-title":"Ataxia with Vitamin E Deficiency May Present with Cervical Dystonia","volume":"6","author":"Becker","year":"2016","journal-title":"Tremor Other Hyperkinetic Mov."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/mus.20144","article-title":"Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease","volume":"31","author":"Kleopa","year":"2005","journal-title":"Muscle Nerve"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e1039","DOI":"10.1542\/peds.2012-2923","article-title":"Spasmodic Muscle Cramps and Weakness as Presenting Symptoms in Wilson Disease","volume":"132","author":"Rosen","year":"2013","journal-title":"Pediatrics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/brain\/awv057","article-title":"PMPCA mutations cause abnormal mitochondrial protein processing in patients with non-progressive cerebellar ataxia","volume":"138","author":"Jobling","year":"2015","journal-title":"Brain"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101193","DOI":"10.1016\/j.omtm.2024.101193","article-title":"AAV8 gene therapy reverses cardiac pathology and prevents early mortality in a mouse model of Friedreich\u2019s ataxia","volume":"32","author":"Chang","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/84818","article-title":"Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits","volume":"27","author":"Puccio","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich\u2019s Ataxia: A Clinical and Genetic Study of 90 Families with an Analysis of Early Diagnostic Criteria and Intrafamilial Clustering of Clinical Features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/ng1097-215","article-title":"Aconitase and mitochondrial iron\u2013sulphur protein deficiency in Friedreich ataxia","volume":"17","author":"Chretien","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e155201","DOI":"10.1172\/jci.insight.155201","article-title":"Frataxin deficiency lowers lean mass and triggers the integrated stress response in skeletal muscle","volume":"7","author":"Dunn","year":"2022","journal-title":"JCI Insight"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e30054","DOI":"10.7554\/eLife.30054","article-title":"Inducible and reversible phenotypes in a novel mouse model of Friedreich\u2019s Ataxia","volume":"6","author":"Chandran","year":"2017","journal-title":"eLife"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1093\/hmg\/ddaa282","article-title":"Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich\u2019s ataxia model mice","volume":"29","author":"Hui","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.ymthe.2018.05.006","article-title":"Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia","volume":"26","author":"Piguet","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/mt.2016.32","article-title":"Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency","volume":"24","author":"Corona","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/sj.mt.6300143","article-title":"Functional recovery in a Friedreich\u2019s ataxia mouse model by frataxin gene transfer using an HSV-1 amplicon vector","volume":"15","author":"Lim","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1089\/hum.2019.363","article-title":"Stress-Induced Mouse Model of the Cardiac Manifestations of Friedreich\u2019s Ataxia Corrected by AAV-mediated Gene Therapy","volume":"31","author":"Salami","year":"2020","journal-title":"Hum. Gene. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"14044","DOI":"10.1038\/mtm.2014.44","article-title":"An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models","volume":"1","author":"Xiao","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41419-020-03359-z","article-title":"Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish","volume":"12","author":"Facchinello","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.devcel.2015.08.006","article-title":"BNIP-H Recruits the Cholinergic Machinery to Neurite Terminals to Promote Acetylcholine Signaling and Neuritogenesis","volume":"34","author":"Sun","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1212\/WNL.0b013e31822e7ca0","article-title":"The natural history of spinocerebellar ataxia type 1, 2, 3, and 6","volume":"77","author":"Jacobi","year":"2011","journal-title":"Neurology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/S1474-4422(15)00202-1","article-title":"Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: A longitudinal cohort study","volume":"14","author":"Jacobi","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e797","DOI":"10.1212\/WNL.0000000000008996","article-title":"Age and sex prevalence estimate of Joubert syndrome in Italy","volume":"94","author":"Nuovo","year":"2020","journal-title":"Neurology"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Cai, L., Huang, X., Ye, Y., Yang, D., Xie, L., Fu, D., Peng, L., Zhou, D., and Liao, J. (2023). Role of gender and age in features of Wilson\u2019s disease. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1176946"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jns.2011.08.028","article-title":"Gender differences in Wilson\u2019s disease","volume":"312","author":"Litwin","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.livres.2017.08.003","article-title":"Wilson disease: At the crossroads between genetics and epigenetics\u2014A review of the evidence","volume":"1","author":"Kieffer","year":"2017","journal-title":"Liver Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6736\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:09:39Z","timestamp":1760033379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":108,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146736"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146736","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]}}}