Founder effect with variable age at onset in Arab families with Lafora disease and EPM2A mutation

Epilepsia. 2007 May;48(5):1011-4. doi: 10.1111/j.1528-1167.2007.01004.x.

Abstract

Purpose: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Arabs / ethnology*
  • Arabs / genetics*
  • Carrier Proteins / genetics*
  • Chromosome Deletion*
  • Family*
  • Female
  • Founder Effect*
  • Gene Frequency / genetics
  • Gene Pool
  • Genotype
  • Haplotypes / genetics
  • Homozygote
  • Humans
  • Israel / epidemiology
  • Lafora Disease / diagnosis*
  • Lafora Disease / epidemiology
  • Lafora Disease / genetics*
  • Male
  • Middle East / epidemiology
  • Mutation / genetics*
  • Pedigree
  • Phenotype

Substances

  • Carrier Proteins
  • EPM2AIP1 protein, human