Familial total anomalous pulmonary venous return with 15q11.2 (BP1-BP2) microdeletion

A 15q11.2 microdeletion (BP1-BP2) is associated with congenital heart diseases (CHDs), developmental delay, and epilepsy. This deletion co-occurs with CHD in 20-30% patients, but a familial case of CHD and a 15q11.2 deletion has not been identified. Here we report the first familial (three siblings) case of total anomalous pulmonary venous return associated with 15q11.2 deletion. Array comparative genomic hybridization identified a ~395 kb deletion at 15q11.2 in patient 1. This deletion was confirmed by fluorescence in situ hybridization in patients 1 and 3 and their asymptomatic father. No deleterious mutation was identified by proband-only exome sequencing of patient 1. One healthy sibling and their mother did not carry the deletion. This deletion is often inherited from asymptomatic parents with an estimated low penetrance of 10.4%. Conversely, we observed high penetrance of this deletion, but secondary copy-number variants or pathogenic variants were not detected in this family.