The SHANK3 Gene was previously linked to the 22Q13 Deletion, in which a portion of the long arm (q) of chromosome 22 is missing. Characterizations include accelerated growth, severly delayed speech, minor dysmorphic features, haploin sufficiency (inability of the gene involved, in this case SHANK3 and PROSAP2, to produces sufficient protein for normal functioning). Studies indicated that the inability to produce sufficient amounts of these proteins may be responsible for most of the neurological symptoms. (For more info. on 22Q13 Deletion, see www.22q13.org) Much of this research was conducted by Dr. Heatehr McDermid (University of Alberta in Canada) and Dr. Katy Phelan of the Greenwood Genetic Center; hence the nickname Phelan-McDermid Syndrome. Testing for these genetic variants are done by ARSA Probes (arylsulfatase A) or FISH (Flourescent In-Situ Hybridization).
In December, 2007, the American Journal of Human Genetics published this article (see abstract below):
Contribution of SHANK3 Mutations to Autism Spectrum Disorder.
Am J Hum Genet. 2007 Dec; 81(6):1289-97.
Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW
Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.