SHANK3
22q13.3 HGNC:14294 Entrez:85358 MIM.606230
SHNAK3 non etiological variations
Some purported disruptive mutation in SHANK3 identified by a commercial genetic testing laboratory can be not an etiological variant. The variant was a 1bp insertion in exon 11 of the RefSeq gene, which we then determined was inherited from a healthy mother and found in 1% of controls. (#21062623#)
Since the variant would be predicted to disrupt the reference gene, and the penetrance of SHANK3 mutations is very high, molecular and bioinformatic analyses concluded that the presumptive exon containing the variant is not likely to be present in most or all SHANK3 transcripts. (#21062623#)
Pathology
severely impaired speech, severe mental retardation, and autistic features consistent with the 22q13.3 deletion syndrome (MIM.606232)
References
Analysis of a purported SHANK3 mutation in a boy with autism: Clinical impact of rare variant research in neurodevelopmental disabilities. Kolevzon A, Cai G, Soorya L, Takahashi N, Grodberg D, Kajiwara Y, Willner JP, Tryfon A, Buxbaum JD. Brain Res. 2010 Nov 6. PMID: #21062623#
Durand, C. M.; Betancur, C.; Boeckers, T. M.; Bockmann, J.; Chaste, P.; Fauchereau, F.; Nygren, G.; Rastam, M.; Gillberg, I. C.; Anckarsater, H.; Sponheim, E.; Goubran-Botros, H.; and 11 others : Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genet. 39: 25-27, 2007. PubMed ID : #17173049#