Neurogenetics

, Volume 9, Issue 2, pp 139–142

Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families

  • Francesca Madia
  • Pasquale Striano
  • Carlo Di Bonaventura
  • Arturo de Falco
  • Fabrizio A. de Falco
  • Mario Manfredi
  • Giorgio Casari
  • Salvatore Striano
  • Carlo Minetti
  • Federico Zara
Short Communication

DOI: 10.1007/s10048-008-0118-4

Cite this article as:
Madia, F., Striano, P., Di Bonaventura, C. et al. Neurogenetics (2008) 9: 139. doi:10.1007/s10048-008-0118-4

Abstract

Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype–phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype “5332” of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype–phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort.

Keywords

BAFMEHaplotypeCortical tremorMyoclonusEpilepsy

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Francesca Madia
    • 1
  • Pasquale Striano
    • 2
    • 3
  • Carlo Di Bonaventura
    • 4
  • Arturo de Falco
    • 5
  • Fabrizio A. de Falco
    • 5
  • Mario Manfredi
    • 4
  • Giorgio Casari
    • 6
  • Salvatore Striano
    • 2
  • Carlo Minetti
    • 3
  • Federico Zara
    • 3
    • 7
  1. 1.Laboratory of Human GeneticsGalliera HospitalsGenoaItaly
  2. 2.Epilepsy Center, Department of Neurological SciencesFederico II UniversityNaplesItaly
  3. 3.Muscular and Neurodegenerative Diseases Unit, “G. Gaslini” InstituteUniversity of GenoaGenoaItaly
  4. 4.Experimental Medicine and Pathology DepartmentlogiaLa Sapienza UniversityRomeItaly
  5. 5.Department of NeurologyLoreto Nuovo HospitalNaplesItaly
  6. 6.Human Molecular Genetics UnitDibit San Raffaele Scientific InstituteMilanItaly
  7. 7.Laboratory of Neurogenetics, Department of Neuroscience“G. Gaslini” Institute, University of GenoaGenoaItaly