Impact Case Study

Uncovering autism genetics in Arabs

Saudi Human Genome Project discovers mutations linked to autism in Saudi families.

12 September 2018

Researchers involved in the Saudi Human Genome Project have identified nearly 50 mutations linked with autism spectrum disorder (ASD) in Saudi Arabian families.  

ASD is a neurodevelopmental disorder characterized by repetitive behaviour patterns and challenges with social interaction and communication. Despite significant research, the causes of ASD remain unclear. More than 600 genes have been linked with ASD to date, but the precise function of many of them remains unknown. Most ASD-related mutations are extremely rare or are specific to a single family or small group, making it difficult to identify general genetic risk factors. 

Researchers at King Faisal Specialist Hospital & Research Center and King Abdulaziz City for Science and Technology sequenced DNA from 19 Saudi Arabians with autism spectrum disorder and their parents. By comparing sequences from the children and parents, the team was able to identify genetic variations linked with ASD. 

Their analysis uncovered 47 mutations in 17 of the families. Many of the mutations were linked with the X chromosome, which is consistent with the fact that ASD is more common in males. 

Since the team had the sequences of the parents and the children, they could distinguish spontaneous mutations in the children from those inherited from their parents. Only three of the mutations were spontaneous; the remainder were already present in the parents. In most cases these mutations were recessive, so the parents were unaffected by ASD. The high frequency of inherited ASD-related genetic variations was unsurprising to the researchers, given the highly consanguineous nature of the Saudi population. 

While 38 of the mutations were new, 32 of them were in genes that have already been linked with ASD. Further analysis revealed that many of the affected genes are involved in neuronal development, though several mutations were in genes whose function is unknown. 

The researchers note that most of the children they studied had several mutations linked with ASD. Furthermore, the mutations affected a range of biological processes in the different individuals, with only a few having mutations that primarily affect neuronal development. Overall, this is in keeping with a genetic model in which ASD is shaped by the cumulative effect of multiple mutations in multiple genes.

While this comprehensive characterization of the genetics of ASD in an Arab population revealed a list of genes and mutations for further study in the Saudi population, it also highlights the complexity and heterogeneity of the disorder’s genetic architecture, even in a consanguineous population.


  1. Al-Mubarak, B., Abouelhoda, M., Omar, A., AlDhalaan, H., Aldosari, M., et al. Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families. Scientific Reports 7, 5679 (2017). | article