{"doi":"10.1007/s12311-024-01723-9","title":"Spinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Spinocerebellar ataxias (SCA) are most frequently due to (CAG)\n                    <jats:sub>n</jats:sub>\n                    (coding for polyglutamine, polyQ) expansions and, less so, to expansion of other oligonucleotide repeats (non-polyQ) or other type of variants (non-repeat expansion SCA). In this study we compared polyQ and non-repeat expansion SCA, in a cohort of patients with hereditary ataxia followed at a tertiary hospital. From a prospective study, 88 patients (51 families) with SCA were selected, 74 (40 families) of whom genetically diagnosed. Thirty-eight patients (51.4%, 19 families) were confirmed as having a polyQ (no other repeat-expansions were identified) and 36 (48.6%, 21 families) a non-repeat expansion SCA. Median age-at-onset was 39.5 [30.0-45.5] for polyQ and 7.0 years [1.00-21.50] for non-repeat expansion SCA. PolyQ SCA were associated with cerebellar onset, and non-repeat expansion forms with non-cerebellar onset. Time to diagnosis was longer for non-repeat expansion SCA. The most common polyQ SCA were Machado-Joseph disease (MJD/SCA3) (73.7%) and SCA2 (15.8%); whereas in non-repeat expansion SCA ATX-\n                    <jats:italic>CACNA1A</jats:italic>\n                    (14.3%),\n                    <jats:italic>ATP1A3</jats:italic>\n                    -related ataxia, ATX-\n                    <jats:italic>ITPR1</jats:italic>\n                    , ATX/HSP-\n                    <jats:italic>KCNA2,</jats:italic>\n                    and ATX-\n                    <jats:italic>PRKCG</jats:italic>\n                    (9.5% each) predominated. Disease duration (up to inclusion) was significantly higher in non-repeat expansion SCA, but the difference in SARA score was not statistically significant. Cerebellar peduncles and pons atrophy were more common in polyQ ataxias, as was axonal neuropathy. SCA had a wide range of genetic etiology, age-at-onset and presentation. Proportion of polyQ and non-repeat expansion SCA was similar; the latter had a higher genetic heterogeneity. While polyQ ataxias were typically linked to cerebellar onset in adulthood, non-repeat expansion forms associated with early onset and non-cerebellar presentations.\n                  </jats:p>","journal":"The Cerebellum","year":2024,"id":628788,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":985324,"name":"Jorge Oliveira","orcid":"0000-0002-9391-5191","position":1,"is_corresponding":false},{"id":1134161,"name":"Mariana Santos","orcid":"0009-0001-8836-2422","position":2,"is_corresponding":false},{"id":1628194,"name":"Sara Costa","orcid":null,"position":3,"is_corresponding":false},{"id":1628195,"name":"Lénia Silva","orcid":null,"position":4,"is_corresponding":false},{"id":1447077,"name":"Carolina Lemos","orcid":"0000-0001-9803-9584","position":5,"is_corresponding":false},{"id":209545,"name":"José Barros","orcid":null,"position":6,"is_corresponding":false},{"id":78702,"name":"Jorge Sequeiros","orcid":"0000-0002-9846-1037","position":7,"is_corresponding":false},{"id":1119722,"name":"Joana Damásio","orcid":"0000-0002-6539-6398","position":8,"is_corresponding":false},{"id":697700,"name":"João Moura","orcid":"0000-0002-7817-0881","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Spinocerebellar Ataxias: Phenotypic Spectrum of PolyQ versus Non-Repeat Expansion Forms","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Spinocerebellar ataxias (SCA) are most frequently due to (CAG)\n                    <jats:sub>n</jats:sub>\n                    (coding for polyglutamine, polyQ) expansions and, less so, to expansion of other oligonucleotide repeats (non-polyQ) or other type of variants (non-repeat expansion SCA). In this study we compared polyQ and non-repeat expansion SCA, in a cohort of patients with hereditary ataxia followed at a tertiary hospital. From a prospective study, 88 patients (51 families) with SCA were selected, 74 (40 families) of whom genetically diagnosed. Thirty-eight patients (51.4%, 19 families) were confirmed as having a polyQ (no other repeat-expansions were identified) and 36 (48.6%, 21 families) a non-repeat expansion SCA. Median age-at-onset was 39.5 [30.0-45.5] for polyQ and 7.0 years [1.00-21.50] for non-repeat expansion SCA. PolyQ SCA were associated with cerebellar onset, and non-repeat expansion forms with non-cerebellar onset. Time to diagnosis was longer for non-repeat expansion SCA. The most common polyQ SCA were Machado-Joseph disease (MJD/SCA3) (73.7%) and SCA2 (15.8%); whereas in non-repeat expansion SCA ATX-\n                    <jats:italic>CACNA1A</jats:italic>\n                    (14.3%),\n                    <jats:italic>ATP1A3</jats:italic>\n                    -related ataxia, ATX-\n                    <jats:italic>ITPR1</jats:italic>\n                    , ATX/HSP-\n                    <jats:italic>KCNA2,</jats:italic>\n                    and ATX-\n                    <jats:italic>PRKCG</jats:italic>\n                    (9.5% each) predominated. Disease duration (up to inclusion) was significantly higher in non-repeat expansion SCA, but the difference in SARA score was not statistically significant. Cerebellar peduncles and pons atrophy were more common in polyQ ataxias, as was axonal neuropathy. SCA had a wide range of genetic etiology, age-at-onset and presentation. Proportion of polyQ and non-repeat expansion SCA was similar; the latter had a higher genetic heterogeneity. While polyQ ataxias were typically linked to cerebellar onset in adulthood, non-repeat expansion forms associated with early onset and non-cerebellar presentations.\n                  </jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39048885","pmcid":"PMC11585503","openalex_id":"https://openalex.org/W4400940416","authors":[],"funders":[{"funder_name":"Universidade do Porto","grant_id":"","title":null}],"total_grants":1,"fwci":0.7682,"citation_percentile":0.67428672,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s12311-024-01723-9.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s12311-024-01723-9.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s12311-024-01723-9/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s12311-024-01723-9","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39048885","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11585503","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11585503/pdf/12311_2024_Article_1723.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11585503","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11585503?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Genetic Neurodegenerative Diseases","Mitochondrial Function and Pathology","DNA Repair Mechanisms"],"mesh_terms":["Adult","Aged","Female","Humans","Male","Middle Aged","Peptides","Phenotype","Prospective Studies","Cohort Studies","Age of Onset","Trinucleotide Repeat Expansion","Spinocerebellar Ataxias","DNA Repeat Expansion","Young Adult"],"keywords":["Spinocerebellar ataxia","Trinucleotide repeat expansion","Machado–Joseph disease","Age of onset","Internal medicine","Medicine","Disease","Biology","Genetics","Allele","Hereditary Ataxia","Machado-joseph Disease","Trinucleotide Repeat Expansions","Hereditary Spinocerebellar Degenerations","Spinocerebellar Diseases"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T15:04:18.918501Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}