Multiple de novo copy number variations in two subjects with developmental problems and multiple congenital anomalies

Background De novo copy number variation (CNV) can occur constitutionally in gametogenesis or in early development leading to sporadic genomic disorders. Such de novo CNVs appear to also be important in somatic mutagenesis relevant to cancer and population events important to species evolution. Since large pathological CNVs are rarely observed at more than one locus in a single patient, and are often de novo, current efforts in understanding their molecular features and underlying mechanisms have relied on comparing CNVs from different individuals. Therefore, knowledge regarding size, mechanism and spatial distribution of de novo genomic rearrangements in a single genetic background is lacking.