title: Autosomal dominant partial epilepsy with auditory features: a new locus on chromosome 19q13.11-q13.31.
abstract: OBJECTIVE
  To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features (ADPEAF) not related to leucine-rich, glioma-inactivated 1 (LGI1) gene.
  
  
  METHODS
  Seventy family members (four married-ins) participating in the study were assessed by a detailed clinical interview and a complete neurologic examination. Genetic mapping was conducted through autosome-wide single nucleotide polymorphism (SNP) genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25 subjects, respectively.
  
  
  RESULTS
  The pedigree comprised 15 affected members, of whom 11 were included in the study (male/female: 6/5; mean age 39.5 years). All but two (III:22 and IV:92) had focal seizures with auditory aura followed by secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was 13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects (8 affected) pointed to a single genomic region on chromosome 19 with a maximum multipoint logarithm of the odds (LOD) score of 2.60. Further refinement of this region through SNP and microsatellite genotyping on 16 subjects (11 affected) increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most likely located in a 9.74 Mb interval between markers D19S416 and D19S420. Sequence analysis of the most prominent candidate genes within this critical interval (SCN1B, LGI4, KCNK6, and LRFN1) did not reveal any mutation.
  
  
  CONCLUSIONS
  This study disclosed a novel ADPEAF locus on chromosome 19q13.11-q13.31, contributing to future identification of a second dominant gene for this epileptic syndrome. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
authors.affiliation: IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bisulli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Naldi
authors.forename: Sara
authors.initials: S
authors.lastname: Baldassari
authors.forename: Pamela
authors.initials: P
authors.lastname: Magini
authors.forename: Laura
authors.initials: L
authors.lastname: Licchetta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Castegnaro
authors.forename: Margherita
authors.initials: M
authors.lastname: Fabbri
authors.forename: Carlotta
authors.initials: C
authors.lastname: Stipa
authors.forename: Simona
authors.initials: S
authors.lastname: Ferrari
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Gilson Edmar
authors.initials: GE
authors.lastname: Gonçalves Silva
authors.forename: Paolo
authors.initials: P
authors.lastname: Tinuper
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pippucci
mesh_terms: D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D017034:Epilepsy, Frontal Lobe / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012893:Sleep Wake Disorders / Q000235:genetics*; D055815:Young Adult
keywords: Auditory aura; Autosomal dominant partial epilepsy with auditory features; Linkage analysis