In conclusion, our results are consistent with the view that TS is genetically a highly heterogeneous disorder, in which rare variants, including de-novo mutations, could underlie a substantial fraction of cases. Recently, Cooper et al (2011) conducted a large-scale study to investigate the role of CNVs in ∼15,000 children with intellectual disability and estimated that ∼14.2% are due to CNVs >400 kb. Similarly, the 7.6% excess of large CNVs in TS patients observed here could be taken as a rough estimate of the proportion of cases that might be caused by CNVs. The analysis of larger TS study samples should enable a more definite assessment of the role of large rearrangements at specific gene regions in this disorder. More extensive surveys of parent-TS offspring trios are also required to estimate the proportion of cases that could be due to highly penetrant de-novo mutations. Finally, sequencing studies should allow a full assessment of the role of rare variants in the aetiology of TS.
