Lafora disease due to EPM2B mutations: a clinical and genetic study.
OBJECTIVE
To study EPM2B gene mutations and genotype-phenotype correlations in patients with Lafora disease.


METHODS
The authors performed a clinical and mutational analysis of 25 patients, from 23 families, diagnosed with Lafora disease who had not shown mutations in the EPM2A gene.


RESULTS
The authors identified 18 mutations in EPM2B, including 12 novel mutations: 4 nonsense mutations (R265X, C26X, W219X, and E67X), a 6-base pair (bp) microdeletion resulting in a two amino acid deletion (V294_K295del), a 4-bp insertion resulting in a frameshift mutation (S339fs12), and 6 missense mutations (D308A, I198N, C68Y, E67Q, P264H, and D233A). In our data set of 77 families with Lafora disease, 54 (70.1%) tested probands have mutations in EPM2A, 21 (27.3%) in EPM2B, and 2 (2.6%) have no mutations in either gene. The course of the disease was longer in patients with EPM2B mutations vs patients with EPM2A mutations.


CONCLUSIONS
Genetic allelic heterogeneity is present in Lafora disease associated with mutations in EPM2B. Patients with mutations in EPM2A and EPM2B express similar clinical manifestation, although patients with EPM2B-associated Lafora disease seem to have a slightly milder clinical course. The lack of mutations in EPM2A and EPM2B in two families could be because of the presence of mutations in noncoding, nontested regions or the existence of an additional gene associated with Lafora disease.
Gómez-Abad
C
C
Neurology Service, Fundación Jiménez Díaz, Madrid, Spain.
Gómez-Garre
P
P
Gutiérrez-Delicado
E
E
Saygi
S
S
Michelucci
R
R
Tassinari
C A
CA
Rodríguez de Córdoba
S
S
Serratosa
J M
JM
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005192:Family Health; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D020192:Lafora Disease / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; C478960:NHLRC1 protein, human; D044767:Ubiquitin-Protein Ligases