{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:43:54Z","timestamp":1788173034417,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,4,16]],"date-time":"2011-04-16T00:00:00Z","timestamp":1302912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Juvenile neuronal ceroid lipofuscinosis (JNCL, NCL3, Batten disease) is usually caused by a 1.02\u2010kb deletion in the <jats:italic>CLN3<\/jats:italic> gene. Mutations in the <jats:italic>CLN1<\/jats:italic> gene may be associated with a variant form of JNCL (vJNCL). We report the clinical course and molecular studies in 24 patients with JNCL collected from 1975 to 2010 with the aim of assessing the natural history of the disorder and phenotype\/genotype correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>Patients were classified into the groups of vJNCL with mutations in the <jats:italic>CLN1<\/jats:italic> gene and\/or granular osmiophilic deposit (GROD) inclusion bodies (n\u2009=\u200911) and classic JNCL (cJNCL) with mutations in the <jats:italic>CLN3<\/jats:italic> gene and\/or fingerprint (FP) profiles (n\u2009=\u200913). Psychomotor impairment included regression of acquired skills, cognitive decline, and clinical manifestations of the disease. We used Kaplan\u2010Meier analyses to estimate the age of onset of psychomotor impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with vJNCL showed learning delay at an earlier age (median 4 years, 95% confidence interval [CI] 3.1\u20134.8) than those in the cJNCL group (median 8 years, 95% CI 6.2\u20139.7) (<jats:italic>P<\/jats:italic>\u2009=\u20090.001) and regression of acquired skills at a younger age. Patients with vJNCL showed a more severe and progressive clinical course than those with cJNCL. There may be a Gypsy ancestry for V181L missense mutation in the <jats:italic>CLN1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The rate of disease progression may be useful to diagnose vJNCL or cJNCL, which should be confirmed by molecular studies in <jats:italic>CLN1<\/jats:italic>\/<jats:italic>CLN3<\/jats:italic> genes. Further studies of genotype\/phenotype correlation will be helpful for understanding the pathogenesis of this disease.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-011-9323-7","type":"journal-article","created":{"date-parts":[[2011,4,15]],"date-time":"2011-04-15T05:33:59Z","timestamp":1302845639000},"page":"1083-1093","source":"Crossref","is-referenced-by-count":28,"title":["Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients"],"prefix":"10.1002","volume":"34","author":[{"given":"Mar\u00eda\u2010Socorro","family":"P\u00e9rez\u2010Poyato","sequence":"first","affiliation":[{"name":"Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III Hospital de Sant Joan de D\u00e9u Esplugues de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Mil\u00e0 Recansens","sequence":"additional","affiliation":[{"name":"Biochemical and Molecular Genetics Department and Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III Hospital Cl\u00ednic, Universitat de Barcelona Barcelona Spain"},{"name":"IDIBAPS, Hospital Cl\u00ednic, Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidre","family":"Ferrer Abizanda","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Montero S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III Hospital de Sant Joan de D\u00e9u Esplugues de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Rodr\u00edguez\u2010Revenga","sequence":"additional","affiliation":[{"name":"Biochemical and Molecular Genetics Department and Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III Hospital Cl\u00ednic, Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Cus\u00ed S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Pathology Hospital de Sant Joan de D\u00e9u Esplugues de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Mar","family":"Garc\u00eda Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Neurology Hospital de Figueres Girona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Domingo Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Neurology Hospital Virgen de la Arrixaca Murcia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Camino Le\u00f3n","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Neurology Hospital Reina Sof\u00eda C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Vel\u00e1zquez Fragua","sequence":"additional","affiliation":[{"name":"Service of Pediatric Neurology Hospital La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Mart\u00ednez\u2010Bermejo","sequence":"additional","affiliation":[{"name":"Service of Pediatric Neurology Hospital La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e8","family":"Pineda Marf\u00e0","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER\u2010ER), Instituto de Salud Carlos III Hospital de Sant Joan de D\u00e9u Esplugues de Llobregat Barcelona Spain"},{"name":"Department of Pediatric Neurology Hospital Sant Joan de D\u00e9u Passeig de Sant Joan de D\u00e9u 2, E\u201008950 Esplugues de Llobregat Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050803"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1999.tb00782.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb04608.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2008.10.012"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-008-0891-x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3112"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100720070043"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9091(96)80031-3"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1998.tb00142.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00499.x"},{"key":"e_1_2_6_12_1","first-page":"128","volume-title":"NCL in different European countries. 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