Clinical and genetic findings in 26 Italian patients with Lafora disease.
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.
Franceschetti
Silvana
S
Department of Clinical Neurophysiology, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Gambardella
Antonio
A
Canafoglia
Laura
L
Striano
Pasquale
P
Lohi
Hannes
H
Gennaro
Elena
E
Ianzano
Leonarda
L
Veggiotti
Pierangelo
P
Sofia
Vito
V
Biondi
Roberto
R
Striano
Salvatore
S
Gellera
Cinzia
C
Annesi
Grazia
G
Madia
Francesca
F
Civitelli
Donata
D
Rocca
Francesca E
FE
Quattrone
Aldo
A
Avanzini
Giuliano
G
Minassian
Berge
B
Zara
Federico
F
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*
D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases