title: Benign adult familial myoclonic epilepsy (BAFME): evidence of an extended founder haplotype on chromosome 2p11.1-q12.2 in five Italian families.
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.
authors.affiliation: Laboratory of Human Genetics, Galliera Hospitals, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bonaventura
authors.forename: Arturo
authors.initials: A
authors.lastname: de Falco
authors.forename: Fabrizio A
authors.initials: FA
authors.lastname: de Falco
authors.forename: Mario
authors.initials: M
authors.lastname: Manfredi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casari
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D005819:Genetic Markers