biostudies-literatureUnknown10(9)Leblond CSSHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extePLoS geneticse1004580https://www.ebi.ac.uk/biostudies/studies/S-EPMC4154644biostudies-literatureMeta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.PMC4154644Huguet GBoeckers TMDelepine MGauthier JLaffargue FLemiere NColeman MDepienne CPerrin LRouleau GAGillberg ICMouzat KLeboyer MBrice AAfenjar ASzatmari PLeblond CSGiuliano FDurand CMHeron DHowe JChiesa JMaestrini EAssouline BSchmeisser MJPeyre HPinto DLumbroso SMathieu ARivier FDevillard FStordeur CTabet ACNava CHolt REdery PBourgeron TGalan PScherer SWDelorme RSanlaville DPolge AGillberg CBonneau DBetancur CGuibert JEy EAmsellem FMonaco APToro RSchluth-Bolard CSato DRastam MJacquette AZelenika DRegnault BRastetter ALespinasse JRappold GALathrop MfalseMeta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an exte2014-01-01T00:00:00Z2014 Sep2026-05-03T23:19:58.283Z2026-04-07T19:45:39.611ZS-EPMC41546442518830010.1371/journal.pgen.1004580