Autism spectrum disorder (ASD) is classified as a neuro-developmental disease with a dramatically increasing prevalence from 4 in 10000 to recently 1 in 68 children. SHANK-3 proteins are multidomain scaffold proteins of the postsynaptic density and also play a role in synapse formation and dendritic spine maturation. Recent human genetic studies suggest the potential association between molecular defects of SHANK-3 and ASD. DTI imaging and TBSS analysis was applied to study how SHANK-3 gene mutation results in severe microstructure of white matter. Results showed significant damage in SHANK-3 group but no positive findings between ASD and typical development controls. These results calls for attention to re-examine the previous neuroimaging studies of ASD or other neuro-developmental diseases where the positive correlations could be contaminated with unexplored genetic mutation influence.