**2. Problem statement**

Despite important advances in molecular genetics, the complete spectrum of the genetic component of ASD is still largely unresolved. There are many possible reasons for this partial lack of success. Among them, the complexity of the Central Nervous System, the relatively unique set of risk factors in each patient, which includes the combined effect of genetic (long/ short, common, rare, and/or de novo sequences), and the interaction with environmental and epigenetic components. Furthermore, the possibility of genetic loci affecting two or more distinct traits or phenotypes (pleiotropy), and an incomplete penetrance (lack of clinical symptoms in individuals who carry risk alleles) also complicate the genetic studies of ASD.

The core symptoms of ASD, differences in intellectual and language abilities, and comorbidity, among other characteristics help highlight the presence of clinical heterogeneity in ASD. Knowledge about variability of genetic, environmental, and epigenetic factors in these disorders, as well as the presence of clinical heterogeneity, has propelled the search for more homogenous groups of patients through the study of potential endophenotypes. They may contribute to facilitate the identification of genetic risk factors and basic molecular mechanisms involved in ASD.
