ADNP-related syndromic ASD seems to be more clinically heterogeneous than existing monogenic syndromes. However, this greater heterogeneity between patients with ADNP mutations might be caused by applying a more unbiased gene identification strategy. Until recently, patients were selected for screening a specific gene based on clinical similarity with an existing disorder. This biased selection procedure increases the chance of detecting a mutation in the target gene in two patients with convincing clinical similarity. In contrast, WES is applied on very large cohorts without phenotypic bias, except for a small set of broad inclusion criteria, such as ASD/ID. The clinical heterogeneity of these cohorts diminishes the chances that identical mutations are found in two or more patients with a strong clinical resemblance. If this hypothesis is correct, the phenotypic spectrum of many existing, clinically well delineated rare disorders is likely to expand in the post-exomic era [Yu et al., 2013].
