title: Autosomal dominant vasovagal syncope: clinical features and linkage to chromosome 15q26.
abstract: OBJECTIVE
  To establish the occurrence of an autosomal dominant form of vasovagal syncope (VVS) by detailed phenotyping of multiplex families and identification of the causative locus.
  
  
  METHODS
  Patients with VVS and a family history of syncope were recruited. A standardized questionnaire was administered to all available family members and medical records were reviewed. Of 44 families recruited, 6 were suggestive of autosomal dominant inheritance. Genome-wide linkage was performed in family A using single nucleotide polymorphism genotyping microarrays. Targeted analysis of chromosome 15q26 with microsatellite markers was implemented in 4 families; 1 family was too small for analysis.
  
  
  RESULTS
  Family A contained 30 affected individuals over 3 generations with a median onset of 8 to 9 years. The other families comprised 4 to 14 affected individuals. Affected individuals reported typical triggers of VVS (sight of blood, injury, medical procedures, prolonged standing, pain, frightening thoughts). The triggers varied considerably within the families. Significant linkage to chromosome 15q26 (logarithm of odds score 3.28) was found in family A. Linkage to this region was excluded in 2 medium-sized families but not in 2 smaller families. Sequence analysis of the candidate genes SLCO3A1, ST8SIA2, and NR2F2 within the linkage interval did not reveal any mutations.
  
  
  CONCLUSIONS
  Familial VVS, inherited in an autosomal dominant manner, may not be rare and has similar features to sporadic VVS. The chromosome 15q26 locus in family A increases the susceptibility to VVS but does not predispose to a particular vasovagal trigger. Linkage analysis in the remaining families established likely genetic heterogeneity.
authors.affiliation: Epilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Australia.
authors.forename: Karl Martin
authors.initials: KM
authors.lastname: Klein
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Bromhead
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Smith
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Corcoran
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.forename: Xenia
authors.initials: X
authors.lastname: Iona
authors.forename: Bree L
authors.initials: BL
authors.lastname: Hodgson
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: McMahon
authors.forename: Kate M
authors.initials: KM
authors.lastname: Lawrence
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004562:Electrocardiography; D004569:Electroencephalography; D005260:Female; D018628:Gene Dosage; D005799:Genes, Dominant; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009010:Monte Carlo Method; D009154:Mutation / Q000502:physiology; D010375:Pedigree; D010641:Phenotype; D019462:Syncope, Vasovagal / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D055815:Young Adult
chemical_list: D004247:DNA