Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals.
SHANK3, which is located at the terminal end of this region, has been repeatedly implicated in other neurodevelopmental disorders and deletion of this gene specifically is thought to cause much of the neurologic symptoms characteristic of PMS.
Cumulative evidence has shown that haploinsufficiency of the SHANK3 gene is a major cause of the neurological symptoms of the 22q13.3 deletion syndrome.
Our analysis therefore supports haploinsufficiency of the gene SHANK3, which codes for a structural protein of the postsynaptic density, as a major causative factor in the neurological symptoms of 22q13 deletion syndrome.