A representation of the relationship between the size of the mutational target and the frequency of disease for disorders caused by de novo mutations. Dashed lines separate different sizes of mutational target. Rounded rectangles represent examples of genes. Disease frequency categories range from extremely rare disorders (that is, only a few cases described) to disorders that occur more commonly within the population (such as intellectual disability, which has a frequency in the general population of more than 1%). Underneath each of these categories an example disorder is given. The lower part shows some of the implicated disease gene(s), ranging from a specific domain in a single gene, to single gene disorders, to multiple gene disorders, to disorders with extreme genetic heterogeneity. From left to right: SET binding protein 1 (SETBP1); dihydroorotate dehydrogenase (DHODH); NADH dehydrogenase (ubiquinone) Fe-S protein 1 (NDUFS1); acyl-CoA dehydrogenase family, member 9 (ACAD9); jumonji, AT rich interactive domain 1C (JARID1C); capicua homolog (CIC); deformed epidermal autoregulatory factor 1 (DEAF1); YY1 transcription factor (YY1); dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1); member RAS oncogene family (RAB39B); synaptic Ras GTPase activating protein 1 (SYNGAP1).
Gilissen et al. Genome Biology 2011 12:228 doi:10.1186/gb-2011-12-9-228