title: Clinical and genetic findings in 26 Italian patients with Lafora disease.
abstract: OBJECTIVE
  EPM2B mutations have been found in a variable proportion of patients with Lafora disease (LD). Genotype-phenotype correlations suggested that EPM2B patients show a slower course of the disease, with delayed age at death, compared with EPM2A patients. We herein report clinical and genetic findings of 26 Italian LD patients.
  
  
  METHODS
  Disease progression was evaluated by means of a disability scale based on residual motor and cognitive functions and daily living and social abilities, at 4 years from the onset. Mutational analysis was performed by sequencing the coding regions of the EPM2A and EPM2B genes.
  
  
  RESULTS
  Age at onset ranged from 8.5 to 18.5 years (mean, 13.7+/-2.6). The mean duration of follow-up was 7.1+/-3.9 years. Daily living activities and social interactions were preserved in five of 24 patients. The remaining patients showed moderate to extremely severe limitations of daily living and social abilities. Sixteen (72%) of 22 families showed mutations in the EPM2B gene, and five (22%), in the EPM2A gene. One family showed no mutations. A novel EPM2B mutation also was identified.
  
  
  CONCLUSIONS
  In our series, EPM2B mutations occurred in 72% of families, thus indicating that EPM2B is the major gene for LD in the Italian population. Moreover, we found that six of 17 EPM2B patients preserved daily living activities and social interactions at 4 years from onset, suggesting a slow disease progression. Additional clinical and functional studies will clarify whether specific mutations may influence the course of the disease in LD patients.
authors.affiliation: Department of Clinical Neurophysiology, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Laura
authors.initials: L
authors.lastname: Canafoglia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Leonarda
authors.initials: L
authors.lastname: Ianzano
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Vito
authors.initials: V
authors.lastname: Sofia
authors.forename: Roberto
authors.initials: R
authors.lastname: Biondi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.forename: Grazia
authors.initials: G
authors.lastname: Annesi
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Donata
authors.initials: D
authors.lastname: Civitelli
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Rocca
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
authors.forename: Giuliano
authors.initials: G
authors.lastname: Avanzini
authors.forename: Berge
authors.initials: B
authors.lastname: Minassian
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007398:Interpersonal Relations; D007558:Italy / Q000208:ethnology; D020192:Lafora Disease / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases; D044465:White People / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases