Methods
During the genetic counselling, informed consent was obtained from all
family members for molecular analysis and publication of the data. DNA
was first extracted from peripheral blood of the index and his affected
sister according to standard protocol. By comparing the whole exome of
the index and of his sister 981 shared variants were identified.
Variants with a low PhyloP value (<2.0, indicating weak
evolutionary conservation) and a high frequency in population databases
(>0.02%) and our in-house database (≥20 hits) were excluded.
This resulted in 27 remaining shared variants, which were further
analysed. Of these 27 variants, only one gene was known to be associated
with cardiac development and valve abnormalities, namely thePDLIM7 gene.