Abstracts

Rationale: We tested the hypothesis that de novo copy number variants (CNVs) or the CNVs implicated in known genomic disorders ("pathogenic CNVs") as described in online mendelian inheritance in man (OMIM) morbid map are significant predisposing factors for infantile spasms. Methods: We performed a genome-wide analysis of single nucleotide polymorphism (SNP) genotyping microarray data to identify the role of de novo/known pathogenic large CNVs in 13 trios of children affected by infantile spasms using the Illumina 610Quad platform. Results: A rare large (4.8 MB) de novo duplication was detected in 15q11-13 region of one patient (Figure 1 A). In addition, 3 known pathogenic CNVs (present in patient as well as one of the parents) were detected in total. In one patient, a known pathogenic deletion was detected in the region of 2q32.3 (Figure 1 B). Similarly, in another patient two known pathogenic deletions in the region of 16p11.2 (Figure 2 A) and Xp22.13 (containing CDKL5) (Figure 2 B) were detected. These two patients were phenotypically different from the patient where the de novo CNV was detected. Conclusions: These findings suggest that some specific pathogenic CNVs predispose to infantile spasms and may be associated with different phenotypes. However, additional modifying factors (genetic and environmental) likely also play an important role in determining the overall phenotype.