Autism spectrum disorders (ASDs) can arise from rare highly penetrant mutations and genomic imbalances. Phelan-McDermid syndrome, due to 22q13.3 deletions involving the synaptic scaffolding gene SHANK3, is one of the more frequently reported chromosomal abnormalities in ASD. It is characterized by intellectual disability and severe language impairment; autism or autistic traits are common. Rare de novo mutations in SHANK3 have been identified in patients with ASD. More recently, de novo intragenic SHANK2 deletions and a mutation were reported in ASD and/or intellectual disability.
Objectives: The molecular and clinical characteristics of patients with mutations in SHANK2 and SHANK3 will be presented. We also review reports in the literature from additional groups.
Methods:
Patients with SHANK mutations were identified through sequencing and gene dosage experiments (FISH, MLPA, and microarray studies). A detailed clinical assessment is performed by clinical geneticists and psychiatrists.
Results:
De novo deletions and mutations in SHANK2 and SHANK3, as well 22q13 duplications including SHANK3 have been reported in patients with ASD and/or intellectual disability. The significance of rare inherited variants in SHANK2 is unclear at present.
Conclusions:
These findings provide further support for the involvement of postsynaptic proteins in the etiology of ASD and intellectual disability and further confirm a common genetic etiology in these two neurodevelopmental disorders.