Genealogical and molecular analysis of a family-based cohort of congenital heart disease patients from the São Miguel Island (Azores, Portugal).

Background: Congenital heart disease (CHD) is one common birth malformation, accounting for ∼30% of total congenital abnormalities.

Aim: 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.

Subjects And 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 (F) 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 F values were found in patients with parental consanguinity (0.0371) and patent ductus arteriosus (0.0277).

Conclusion: 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.