A study headed by Jacques Michaud from the University of Montreal identified a de novo splice site mutation in the SHANK3 gene in a boy with mild intellectual disability. This mutation changes the assembly of the protein during its synthesis and leads to a truncation of the longest forms of SHANK3. This truncation occurs at the beginning of the molecule in a domain called the ankyrin repeat domain. The mutation specifically disrupts the longest forms of SHANK3 and shows that loss of even these longer forms are sufficient to produce neurodevelopmental disability. Interestingly, the mouse model published by Bozdagi et al in 2010 has a very similar (though not identical) mutation. The study from the Michaud group was published in the American Journal of Human Genetics.
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