{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:02:40Z","timestamp":1790197360560,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Most individuals with Friedreich ataxia (FRDA) have homozygous GAA triplet repeat expansions in the <jats:italic>FXN<\/jats:italic> gene, correlating with a typical phenotype of ataxia and cardiomyopathy. A minority are compound heterozygotes carrying a GAA expansion on one allele and a mutation on the other. The study aim was to examine phenotypic variation among compound heterozygotes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data on <jats:italic>FXN<\/jats:italic> mutations were obtained from the Friedreich Ataxia Clinical Outcome Measures Study (FA\u2010COMS). We compared clinical features in a single\u2010site FA\u2010COMS cohort of 51 compound heterozygous and 358 homozygous patients, including quantitative measures of cardiac, neurologic, and visual disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Non\u2010GAA repeat mutations were associated with reduced cardiac disease, and patients with minimal\/no function mutations otherwise had a typical FRDA phenotype but with significantly more severe progression. The partial function mutation group was characterized by relative sparing of bulbar and upper limb function, as well as particularly low cardiac involvement. Other clinical features in this group, including optic atrophy and diabetes mellitus, varied widely depending on the specific type of partial function mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These data support that the typical FRDA phenotype is driven by frataxin deficiency, especially severe in compound heterozygotes with minimal\/no function mutations, whereas the heterogeneous presentations of those with partial function mutations may indicate other contributing factors to FRDA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52027","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T03:32:40Z","timestamp":1708745560000},"page":"1110-1121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phenotypic variation of <i>FXN<\/i> compound heterozygotes in a Friedreich ataxia cohort"],"prefix":"10.1002","volume":"11","author":[{"given":"Megan M.","family":"Shen","sequence":"first","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine, University of Pennsylvania.  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-911X","authenticated-orcid":false,"given":"Christian","family":"Rummey","sequence":"additional","affiliation":[{"name":"Clinical Data Science GmbH  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-214X","authenticated-orcid":false,"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Perelman School of Medicine, University of Pennsylvania.  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-51892-7.00017-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/nmt-2022-0011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448230"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004399900201"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24595"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-007-0101-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.11.e38"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100480050037"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199902)45:2<200::AID-ANA10>3.0.CO;2-U"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12317"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.5.661"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.2.496"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-019-00594-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100043778"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-002-0902-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1771"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.07.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.433"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm038"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp592"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgac142"},{"issue":"2","key":"e_1_2_8_23_1","first-page":"425","article-title":"Protein mutations and stability, a link with disease: the case study of frataxin","volume":"10","author":"Puglisi R","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.728"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi200666h"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.435263"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.332"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.225"},{"issue":"2","key":"e_1_2_8_29_1","first-page":"267","article-title":"Gender specificities of cardiac troponin serum levels: from formation mechanisms to the diagnostic role in case of acute coronary syndrome","volume":"13","author":"Chaulin AM","year":"2023","journal-title":"Life (Basel)"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51830"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200913"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29370"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:6<506::AID-HUMU20>3.0.CO;2-E"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-009-0233-x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/tomography7040076"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1855"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.05.023"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.059477"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v11.i1.1"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448535"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx047"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448461"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.04.159"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9061630"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.09.025"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.04.005"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.05.074"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2021.10.010"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2021.02.032"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.01.004"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:43:43Z","timestamp":1715705023000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,23]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/acn3.52027"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52027","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,23]]},"assertion":[{"value":"2023-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}