title: Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy.
abstract: BACKGROUND
  To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations.
  
  
  METHODS
  A cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively.
  
  
  RESULTS
  One hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7% of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8% of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5%). Juvenile onset NCL patients accounted for 17.7% of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5% of the CLN2 and 78.6% of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000.
  
  
  CONCLUSIONS
  Descriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.
authors: Department of Neurological, Neuropsychological, Morphological, Motor Sciences, University of Verona, Verona, Italy.
authors: Filippo Maria
authors: FM
authors: Santorelli
authors: Barbara
authors: B
authors: Garavaglia
authors: Francesco
authors: F
authors: Cardona
authors: Nardo
authors: N
authors: Nardocci
authors: Bernardo Dalla
authors: BD
authors: Bernardina
authors: Stefano
authors: S
authors: Sartori
authors: Agnese
authors: A
authors: Suppiej
authors: Enrico
authors: E
authors: Bertini
authors: Dianela
authors: D
authors: Claps
authors: Roberta
authors: R
authors: Battini
authors: Roberta
authors: R
authors: Biancheri
authors: Mirella
authors: M
authors: Filocamo
authors: Francesco
authors: F
authors: Pezzini
authors: Alessandro
authors: A
authors: Simonati
mesh_terms: D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D017720:Molecular Epidemiology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000453:epidemiology*; D000091346:Tripeptidyl-Peptidase 1
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