title: Genealogical and molecular analysis of a family-based cohort of congenital heart disease patients from the São Miguel Island (Azores, Portugal).
abstract: BACKGROUND
  Congenital heart disease (CHD) is one common birth malformation, accounting for ∼30% of total congenital abnormalities.
  
  
  OBJECTIVE
  Considering the unknown role of consanguinity in causing CHD, this study hypothesised that consanguineous unions and/or familial aggregation may be frequent in the Azorean Island of São Miguel (Portugal). To that end, a retrospective observational study was performed based on genealogical and molecular analyses.
  
  
  METHODS
  The study enrolled 112 CHD patients from São Miguel Island, which allowed the assessment of type of family (simplex or multiplex), parental consanguinity and grandparental endogamy. Based on 15 STR markers, inbreeding coefficients (FIS) in the CHD cohort and healthy control group (n = 114) were estimated.
  
  
  RESULTS
  Multiplex families were 37.6% (n = 41/109), a rate considerably higher than previously described in the literature (< 15%). Moreover, 9.2% (n = 10/109) of the CHD families were consanguineous, mostly derived from third cousin unions, and 20.2% (n = 22/109) presented full grandparental endogamy. Higher FISvalues were found in patients with parental consanguinity (0.0371) and patent ductus arteriosus (0.0277).
  
  
  CONCLUSIONS
  This study analysed several genealogical and genetic features related with CHD, revealing the presence of parental consanguinity and extensive familial aggregation in the CHD patients from São Miguel Island.
authors.affiliation: a Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE , São Miguel Island, Azores , Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Cabral
authors.affiliation: a Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE , São Miguel Island, Azores , Portugal.|b Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisboa , Portugal.
authors.forename: Renato
authors.initials: R
authors.lastname: Pires
authors.affiliation: c Department of Pediatric Cardiology , Hospital of Santa Cruz , Carnaxide , Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Anjos
authors.affiliation: a Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE , São Miguel Island, Azores , Portugal.|b Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisboa , Portugal.|d Instituto Gulbenkian de Ciência , Oeiras , Portugal , and.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Branco
authors.affiliation: e Department of Pediatrics , Hospital of Divino Espírito Santo of Ponta Delgada, EPE , São Miguel Island, Azores , Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Maciel
authors.affiliation: a Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada, EPE , São Miguel Island, Azores , Portugal.|b Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisboa , Portugal.|d Instituto Gulbenkian de Ciência , Oeiras , Portugal , and.
authors.forename: Luisa
authors.initials: L
authors.lastname: Mota-Vieira
mesh_terms: D001394:Azores; D016022:Case-Control Studies; D015331:Cohort Studies; D003241:Consanguinity; D005190:Family; D005260:Female; D005789:Genealogy and Heraldry; D014644:Genetic Variation; D000066502:Grandparents; D006330:Heart Defects, Congenital / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010290:Parents; D011174:Portugal
keywords: Congenital heart disease; endogamy; familial aggregation; parental consanguinity