title: Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families.
abstract: OBJECTIVE
  Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis.
  
  
  METHODS
  Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models.
  
  
  RESULTS
  Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity.
  
  
  CONCLUSIONS
  Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.
authors.affiliation: Laboratory of Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Istituto G. Gaslini, University of Genova, Genova, and Division of Neurology, Ospedale Pediatrico Bambino Gesù, Roma, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Lispi
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.forename: Monica
authors.initials: M
authors.lastname: Traverso
authors.forename: Laura
authors.initials: L
authors.lastname: Bordo
authors.forename: Paolo
authors.initials: P
authors.lastname: Aridon
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.forename: Baldassare
authors.initials: B
authors.lastname: Barone
authors.forename: Bernardo
authors.initials: B
authors.lastname: dalla Bernardina
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Capovilla
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Marco
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaggero
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: Ruth
authors.initials: R
authors.lastname: Day
authors.forename: Francesca
authors.initials: F
authors.lastname: Vanadia
authors.forename: Marilena
authors.initials: M
authors.lastname: Vecchi
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Veggiotti
authors.forename: Federico
authors.initials: F
authors.lastname: Vigevano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viri
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004569:Electroencephalography / Q000706:statistics & numerical data; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics*; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D010375:Pedigree; D019683:Penetrance; D014057:Tomography, X-Ray Computed