{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T18:46:54Z","timestamp":1768675614283,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction and objectives<\/jats:title><jats:p>Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical\u2010radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still less than 50%. Our objective was to develop and explore the usefulness of a new diagnostic procedure using standardized molecular diagnostic tools, and next\u2010generation sequencing techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A prospective, observational, analytical study was conducted in a cohort of 46 patients, evaluated between May 2008 and December 2016, with a suspected genetic leukoencephalopathy or leukodystrophy. A diagnostic procedure was set up using classical monogenic tools in patients with characteristic phenotypes, and next\u2010generation techniques in nonspecific ones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Global diagnostic procedure yield was 57.9%, identifying the etiological pathogenesis in 22 of the 38 studied subjects. Analysis by subgroups, Sanger method, and next\u2010generation sequencing showed a yield of 64%, and 46.1% respectively. The most common pathologies were adrenoleukodystrophy, cerebral autosomal\u2010dominant arteriopathy with subcortical infarcts (CADASIL), and vanishing white matter disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results confirm the usefulness of the proposed diagnostic procedure expressed in a high diagnostic yield and suggest a more optimal cost\u2010effectiveness in an etiological analysis phase.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12345","type":"journal-article","created":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T14:47:21Z","timestamp":1565966841000},"page":"11-28","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Argentinian clinical genomics in a leukodystrophies and genetic leukoencephalopathies cohort: Diagnostic yield in our first 9 years"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9093-2834","authenticated-orcid":false,"given":"Leila","family":"Cohen","sequence":"first","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Analisa","family":"Man\u00edn","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Medina","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Rodr\u00edguez\u2010Quiroga","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Movements Disorders Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Gonz\u00e1lez\u2010Mor\u00f3n","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neuroophthalmology Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julieta","family":"Rosales","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hernan","family":"Amartino","sequence":"additional","affiliation":[{"name":"Child Neurology Department Hospital Universitario Austral  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norma","family":"Specola","sequence":"additional","affiliation":[{"name":"Metabolism Department Hospital de Ni\u00f1os \u201cSor Mar\u00eda Ludovica\u201d de La Plata  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"C\u00f3rdoba","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Kauffman","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"},{"name":"Instituto de Investigaciones en Medicina Traslacional\u2010CONICET y Facultad de Ciencias Biom\u00e9dicas\u2010Universidad Austral  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Vega","sequence":"additional","affiliation":[{"name":"Neurogenetic Section, Neurology Department, Hospital J.M. Ramos Mej\u00eda, CABA, Centro Universitario de Neurolog\u00eda, Facultad de Medicina Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052635"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1991.tb14833.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1998.2779"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12719"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuarg.2014.03.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191228"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1331.1998.530219.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1014096112916"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1386769"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuarg.2016.05.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1588020"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1370040"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02265264"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx045"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.12.434"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.000412"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37215"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672315000087"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13027"},{"issue":"3","key":"e_1_2_10_22_1","first-page":"11.10.1","article-title":"From FastQ data to high confidence variant calls: The Genome Analysis Toolkit best practices pipeline","volume":"4","author":"Van der Auwera G. A.","year":"2013","journal-title":"Current Protocols in Bioinformatics"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10112"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.01.006"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35936"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.12345","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:57:09Z","timestamp":1693616229000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,16]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/ahg.12345"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12345","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,16]]},"assertion":[{"value":"2018-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}