{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:13:14Z","timestamp":1776445994877,"version":"3.51.2"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype\u2013phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the\n                    <jats:italic>CYP27A1<\/jats:italic>\n                    gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10\u2009years (interquartile range 6.9 to 11\u2009years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.\n                  <\/jats:p>","DOI":"10.1111\/cge.14602","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T04:19:47Z","timestamp":1722831587000},"page":"721-732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinicogenetic characterization of cerebrotendinous xanthomatosis in Brazil"],"prefix":"10.1111","volume":"106","author":[{"given":"Helena","family":"Fussiger","sequence":"first","affiliation":[{"name":"Graduate Program in Medicine: Medical Sciences Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro Lucas G. S. B.","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Federal University of Ceara  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo V. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Neurometabolic Unit, Division of Neuromuscular Diseases, Department of Neurology and Neurosurgery Federal University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-2539","authenticated-orcid":false,"given":"Fernando","family":"Freua","sequence":"additional","affiliation":[{"name":"Clinics Hospital, Faculty of Medicine University of Sao Paulo  S\u00e3o Paulo Brazil"},{"name":"Neurology Department Benefic\u00eancia Portuguesa Hospital  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonette S. E.","family":"Husny","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Bettina Ferro de Souza Universidade Federal do Par\u00e1  Bel\u00e9m Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Em\u00edlia K. E. A.","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"University Hospital Complex Prof. Edgard Santos Universidade Federal da Bahia  Salvador Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Braga\u2010Neto","sequence":"additional","affiliation":[{"name":"Division of Neurology Federal University of Ceara  Fortaleza Brazil"},{"name":"Center of Health Sciences State University of Ceara  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[{"name":"Neurogenetics Unit, Department of Neurology School of Medicine of Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease UCL Institute of Neurology  London UK"},{"name":"The Leonard Wolfson Experimental Neurology Centre National Hospital for Neurology &amp; Neurosurgery  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-6573","authenticated-orcid":false,"given":"Jonas A. M.","family":"Saute","sequence":"additional","affiliation":[{"name":"Graduate Program in Medicine: Medical Sciences Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Medical Genetics Service Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"},{"name":"Neurology Service Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"},{"name":"Department of Internal Medicine Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo R.","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"Division of Neurology Federal University of Ceara  Fortaleza Brazil"},{"name":"Campus Parque Ecol\u00f3gico Centro Universit\u00e1rio Christus  Fortaleza Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.RV17055"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40673-021-00128-2"},{"key":"e_1_2_11_4_1","first-page":"69","article-title":"Une deuxieme observation de cholesterinose tendineuse avec symptomes cerebraux","volume":"42","author":"Van Bogaert L","year":"1937","journal-title":"Ann Med"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320100209"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.10.010"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01980-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-017-0389-4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0093-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjrcr.20190047"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100007X200173"},{"key":"e_1_2_11_12_1","unstructured":"Franklin [online].https:\/\/franklin.genoox.com\/clinical-db\/home. Accessed December 2 2023"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_14_1","first-page":"907","article-title":"Cerebrotendinous xanthomatosis in the Israeli Druze: molecular genetics and phenotypic characteristics","volume":"55","author":"Leitersdorf E","year":"1994","journal-title":"Am J Hum Genet"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108493"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-021-00714-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201112"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006731"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.06.008"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8440-0"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0419-x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9873-1"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6630-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e318288076a"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03439.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.5.908"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14280"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02578-1"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075145"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.10.027"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nrleng.2010.12.002"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-013-9674-3"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2020.12.004"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2013.76"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000506770"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.8.1589"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.1.121"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.217.3.r00dc03869"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050818"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198412273112601"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.04.006"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14230"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T21:57:30Z","timestamp":1730671050000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,5]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/cge.14602"],"URL":"https:\/\/doi.org\/10.1111\/cge.14602","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14602\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14602\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,5]]},"assertion":[{"value":"2024-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}