Samuel Taylor, a PhD student in Dr Laura Andreae’s lab, has recently published his findings in Stem Cell Research & Therapy that haploinsufficiency of autism risk gene SHANK3 could represent an important early abnormality in autism pathogenesis.
Deletions and mutations in SHANK3 have been identified in autism spectrum disorder (ASD). The protein plays a role in synaptic functioning and acts as a scaffold that supports connections between neurons. Targeting the SHANK3 transcript, Samuel performed single-molecule fluorescence in-situ hybridisation (smFISH) in human inducible pluripotent stem cell (hiPSC)-derived cortical neurons. They showed that there was a 50% reduction in SHANK3 mRNA transcripts within neuronal processes in neurons derived from a person with ASD and heterozygous for SHANK3.
These exciting results suggest that local, dendritic targeting of SHANK3 mRNA may be specifically affected in people with SHANK3 haploinsufficiency. The authors look to probe these findings further to fully demonstrate the important early role of SHANK3 in ASD.
For more information, see https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-0957-3