title: Familial ventricular aneurysms and septal defects map to chromosome 10p15.
abstract: OBJECTIVE
  Although ventricular septal defects (VSD) are the most common congenital heart lesion, familial clustering has been described only in rare instances. The aim of this study was to identify genetic factors and chromosomal regions contributing to VSD.
  
  
  RESULTS
  A unique, large kindred segregating various forms of septal pathologies-including VSD, ventricular septal aneurysms, and atrial septal defects (ASD)-was ascertained and characterized clinically and genetically. Eighteen family members in three generations could be studied, out of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of Fallot). Parametric multipoint LOD scores reach significance on chromosome 10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor region where deletions have been reported to associate with septal defects, but that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage analysis scenarios suggest that tetralogy of Fallot is a phenocopy and genetically distinct from the autosomal dominant form of septal pathologies observed in this family.
  
  
  CONCLUSIONS
  This study maps a rare familial form of VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic heterogeneity of septal pathologies. Fine mapping, haplotype construction, and resequencing will provide a unique opportunity to study the pathogenesis of septal defects and shed light on molecular mechanisms of septal development.
authors.affiliation: Cardiovascular Genetics, Department of Pediatrics, Research Center, Centre Hospitalier Universitaire Sainte Justine, University of Montréal, Montréal, QC, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tremblay
authors.forename: Shi Wei
authors.initials: SW
authors.lastname: Yang
authors.forename: Marc-Phillip
authors.initials: MP
authors.lastname: Hitz
authors.forename: Géraldine
authors.initials: G
authors.lastname: Asselin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ginns
authors.forename: Kathleen
authors.initials: K
authors.lastname: Riopel
authors.forename: Roxanne
authors.initials: R
authors.lastname: Gendron
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Edwina
authors.initials: E
authors.lastname: Duhig
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Dorothy
authors.initials: D
authors.lastname: Radford
authors.forename: Gregor
authors.initials: G
authors.lastname: Andelfinger
mesh_terms: D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006322:Heart Aneurysm / Q000235:genetics*; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D013771:Tetralogy of Fallot / Q000235:genetics