Founder effect with variable age at onset in Arab families with Lafora disease and EPM2A mutation.
OBJECTIVE
We observed three apparently unrelated and geographically separate Arab families with Lafora disease in Israel and the Palestinian territories.


METHODS
We clinically evaluated the families and analyzed their DNA for EPM2A mutations.


RESULTS
Of seven individuals with Lafora disease, the clinical onset varied from 13 to 20 years. All three families shared the same novel homozygous deletion in EPM2A. Haplotype analysis around the deletion showed that the families shared a common homozygous haplotype. The boundaries of this haplotype varied between families and even within one family.


CONCLUSIONS
We conclude that considerable variability in the age at onset of Lafora disease can occur within families. Identical mutations can be associated with the classic adolescent presentation, as well as late-onset cases. Haplotype analysis suggests that this EPM2A mutation arose many generations previously, so it may be of importance for cases distributed more widely in the Middle East.
Gomez-Abad
Cristina
C
Neurology Service, Fundación Jiménez Díaz, Madrid, Spain.
Afawi
Zaid
Z
Korczyn
Amos D
AD
Misk
Adel
A
Shalev
Stavit A
SA
Spiegel
Ronen
R
Lerman-Sagie
Tally
T
Lev
Dorit
D
Kron
Katherine L
KL
Gómez-Garre
Pilar
P
Serratosa
Jose M
JM
Berkovic
Samuel F
SF
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D018912:Arabs / Q000208:ethnology* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002872:Chromosome Deletion; D005190:Family; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics; D005788:Gene Pool; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D020192:Lafora Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008877:Middle East / Q000453:epidemiology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
D002352:Carrier Proteins; C483189:EPM2AIP1 protein, human