Figure 2.

CNVs associated with TOF. (a) Duplications in four TOF patients (749, 201.670, 200.430, 200.250) and a deletion (patient 3701) overlap a 875,266 bp region at 1q21 (chr1:144,965,244-145,840,510) which encompasses six known genes that are expressed in the human right ventricular outflow tract. Previously described duplications at this locus are associated with mental retardation (MR)²¹, TOF¹⁶, macrocephaly (MaC)²² and other congenital phenotypes²³. Studies have identified multiple patients (number of patients in parentheses, only the minimal overlapping region between patients is shown) that carry deletions at this locus with congenital heart disease other than TOF (CHD), MR, schizophrenia (SCZ), microcephaly (MiC) or that carry deletions with CHD and MR. (b) Plot showing normalized probe intensity measurements across 1q21 in the four TOF patients carrying a deletion (turquoise), the one TOF patient with a duplication (green) and 273 CN-neutral controls (gray lines and summarized as mean (black) ± 2*median absolute deviation (dark blue lines). The vertical dotted lines indicate the boundaries of the 875,266 bp overlapping region. The absence of circles on the colored lines indicates an absence of probes due to segmental duplications and there is a known CNP downstream of our region of interest. (c) A 12,380,330 bp duplication on chromosome 3 was found in a single TOF patient (756) and an inherited duplication was found within this interval in patient 419 which narrows the interval to a region (chr3:12,605,755-12,781,130) affecting RAF1. White bars indicate deletion, black bars indicate duplication, and red bars indicate the region of overlap between TOF CNVs. Chromosome position is indicated in Mb by the blue bar. All coordinates are based on build 36.1 of the human reference genome.