title: Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients.
abstract: BACKGROUND
  Juvenile neuronal ceroid lipofuscinosis (JNCL, NCL3, Batten disease) is usually caused by a 1.02-kb deletion in the CLN3 gene. Mutations in the CLN1 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.
  
  
  METHODS
  Patients were classified into the groups of vJNCL with mutations in the CLN1 gene and/or granular osmiophilic deposit (GROD) inclusion bodies (n = 11) and classic JNCL (cJNCL) with mutations in the CLN3 gene and/or fingerprint (FP) profiles (n = 13). Psychomotor impairment included regression of acquired skills, cognitive decline, and clinical manifestations of the disease. We used Kaplan-Meier analyses to estimate the age of onset of psychomotor impairment.
  
  
  RESULTS
  Patients with vJNCL showed learning delay at an earlier age (median 4 years, 95% confidence interval [CI] 3.1-4.8) than those in the cJNCL group (median 8 years, 95% CI 6.2-9.7) (P = 0.001) 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 CLN1 gene.
  
  
  CONCLUSIONS
  The rate of disease progression may be useful to diagnose vJNCL or cJNCL, which should be confirmed by molecular studies in CLN1/CLN3 genes. Further studies of genotype/phenotype correlation will be helpful for understanding the pathogenesis of this disease.
authors.affiliation: Departments of Pediatric Neurology and Clinical Biochemistry and Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Hospital de Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain.
authors.forename: María-Socorro
authors.initials: MS
authors.lastname: Pérez-Poyato
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà Recansens
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer Abizanda
authors.forename: Raquel
authors.initials: R
authors.lastname: Montero Sánchez
authors.forename: Laia
authors.initials: L
authors.lastname: Rodríguez-Revenga
authors.forename: Victoria
authors.initials: V
authors.lastname: Cusí Sánchez
authors.forename: M Mar
authors.initials: MM
authors.lastname: García González
authors.forename: Rosario
authors.initials: R
authors.lastname: Domingo Jiménez
authors.forename: Rafael
authors.initials: R
authors.lastname: Camino León
authors.forename: Ramón
authors.initials: R
authors.lastname: Velázquez Fragua
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez-Bermejo
authors.forename: Mercè
authors.initials: M
authors.lastname: Pineda Marfà
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003071:Cognition / Q000502:physiology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005828:Genetics, Population; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000453:epidemiology / Q000209:etiology; D025202:Molecular Diagnostic Techniques; D009472:Neuronal Ceroid-Lipofuscinoses / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D013030:Spain / Q000453:epidemiology; D055815:Young Adult