title: A novel pedigree with familial cortical myoclonic tremor and epilepsy (FCMTE): clinical characterization, refinement of the FCMTE2 locus, and confirmation of a founder haplotype.
abstract: OBJECTIVE
  We describe the clinical, neurophysiologic, and genetic features of a new, large family with familial cortical myoclonic tremor and epilepsy (FCMTE).
  
  
  METHODS
  Reliable clinical information was obtained on the 127 members. Thirty-one collaborative individuals were assessed by a detailed clinical interview and a complete neurologic examination. A polygraphic study was conducted in 15 patients, back-averaging analysis and somatosensory evoked potentials with C-reflex study in four. The genetic study investigated 30 subjects with microsatellite markers at three loci on chromosomes 8q (FCMTE1), 2p (FCMTE2), and 5p (FCMTE3).
  
  
  RESULTS
  The pedigree included 25 affected members (M/F: 9/16). We studied 16 of the 19 living affected members (M/F: 5/11; mean age 47.8 years). Cortical myoclonic tremor (CMT) was associated with generalized seizures in 10 patients (62.5%). The mean age at onset of CMT and seizures was 28.1 and 33.8 years, respectively. Four patients (25%) reported a slow progression of CMT, with severe gait impairment in one. Psychiatric disorders of variable severity recurred in 37.5% of cases. Rhythmic bursts at 7-15 Hz were recorded in all 11 affected members tested. Additional neurophysiologic investigations disclosed a cortical origin of myoclonus in all patients tested. Generalized epileptiform discharges were recorded in 25% of cases, and a photoparoxysmal response in 31%. Genetic analysis established linkage to the FCMTE2 locus on chromosome 2p11.1-2q12.2 (OMIM 607876) and narrowed the critical interval to a 10.4 Mb segment. Haplotype analysis in the present family identified a founder haplotype identical to that previously observed in families from the same geographic area.
  
  
  CONCLUSIONS
  This study confirms evidence of a founder effect in Italian families and reduces the number of positional candidate genes in the FCMTE2 locus to 59, thereby contributing to future gene identification by Next Generation Sequencing approaches.
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Licchetta
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pippucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Bisulli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Cantalupo
authors.forename: Pamela
authors.initials: P
authors.lastname: Magini
authors.forename: Lara
authors.initials: L
authors.lastname: Alvisi
authors.forename: Sara
authors.initials: S
authors.lastname: Baldassari
authors.forename: Paolo
authors.initials: P
authors.lastname: Martinelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Naldi
authors.forename: Nicola
authors.initials: N
authors.lastname: Vanni
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004569:Electroencephalography; D004576:Electromyography; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics*; D005073:Evoked Potentials, Somatosensory / Q000235:genetics; D005260:Female; D020234:Gait Ataxia / Q000209:etiology; D008040:Genetic Linkage; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D055815:Young Adult
keywords: Autosomal dominant myoclonic epilepsy; Cortical tremor; Familial cortical myoclonic tremor and epilepsy