X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3

We report on a Lebanese family in which two maternal cousins suffered and d ied very early in life from cardiac malformations. Both presented with a tr ansposition of the great arteries associated with one or several other card iac defects. Various minor midline defects were also observed, but there we re no situs abnormalities other than a persistent left superior vena cava i n one, A maternal uncle of these two babies was born cyanotic and died on t he third post-natal day. Analysis of the ZIC3 gene, revealed the presence o f a mutation in the second exon leading to a truncation of the protein, Sur prisingly, another maternal uncle of the two affected cousins also had the mutation but was not clinically affected. To our knowledge, this is the fir st instance of incomplete penetrance in a male for a mutation in a chromoso me X gene.