Matches in SemOpenAlex for { <https://semopenalex.org/work/W2069894028> ?p ?o ?g. }
- W2069894028 endingPage "1498" @default.
- W2069894028 startingPage "1489" @default.
- W2069894028 abstract "Recent genetic data on schizophrenia (SCZ) have suggested that proteins of the postsynaptic density of excitatory synapses have a role in its etiology. Mutations in the three SHANK genes encoding for postsynaptic scaffolding proteins have been shown to represent risk factors for autism spectrum disorders and other neurodevelopmental disorders. To address if SHANK2 variants are associated with SCZ, we sequenced SHANK2 in 481 patients and 659 unaffected individuals. We identified a significant increase in the number of rare (minor allele frequency<1%) SHANK2 missense variants in SCZ individuals (6.9%) compared with controls (3.9%, P=0.039). Four out of fifteen non-synonymous variants identified in the SCZ cohort (S610Y, R958S, P1119T and A1731S) were selected for functional analysis. Overexpression and knockdown-rescue experiments were carried out in cultured primary hippocampal neurons with a major focus on the analysis of morphological changes. Furthermore, the effect on actin polymerization in fibroblast cell lines was investigated. All four variants revealed functional impairment to various degrees, as a consequence of alterations in spine volume and clustering at synapses and an overall loss of presynaptic contacts. The A1731S variant was identified in four unrelated SCZ patients (0.83%) but not in any of the sequenced controls and public databases (P=4.6 × 10(-5)). Patients with the A1731S variant share an early prodromal phase with an insidious onset of psychiatric symptoms. A1731S overexpression strongly decreased the SHANK2-Bassoon-positive synapse number and diminished the F/G-actin ratio. Our results strongly suggest a causative role of rare SHANK2 variants in SCZ and underline the contribution of SHANK2 gene mutations in a variety of neuropsychiatric disorders." @default.
- W2069894028 created "2016-06-24" @default.
- W2069894028 creator A5008405084 @default.
- W2069894028 creator A5011462407 @default.
- W2069894028 creator A5013488851 @default.
- W2069894028 creator A5018770490 @default.
- W2069894028 creator A5046972979 @default.
- W2069894028 creator A5048757004 @default.
- W2069894028 creator A5052376806 @default.
- W2069894028 creator A5067791805 @default.
- W2069894028 creator A5078644907 @default.
- W2069894028 creator A5079118201 @default.
- W2069894028 creator A5080507023 @default.
- W2069894028 creator A5088685359 @default.
- W2069894028 creator A5091088506 @default.
- W2069894028 date "2015-01-06" @default.
- W2069894028 modified "2023-10-17" @default.
- W2069894028 title "Identification and functional characterization of rare SHANK2 variants in schizophrenia" @default.
- W2069894028 cites W1580592479 @default.
- W2069894028 cites W1897589155 @default.
- W2069894028 cites W1965509311 @default.
- W2069894028 cites W1966097738 @default.
- W2069894028 cites W1970473240 @default.
- W2069894028 cites W1973138133 @default.
- W2069894028 cites W1976555450 @default.
- W2069894028 cites W1978075999 @default.
- W2069894028 cites W1983194657 @default.
- W2069894028 cites W1983301798 @default.
- W2069894028 cites W1983769138 @default.
- W2069894028 cites W1992086025 @default.
- W2069894028 cites W1994938811 @default.
- W2069894028 cites W1997031801 @default.
- W2069894028 cites W2001188663 @default.
- W2069894028 cites W2003283154 @default.
- W2069894028 cites W2014596655 @default.
- W2069894028 cites W2014906153 @default.
- W2069894028 cites W2017523094 @default.
- W2069894028 cites W2017826413 @default.
- W2069894028 cites W2018643157 @default.
- W2069894028 cites W2019873695 @default.
- W2069894028 cites W2020331089 @default.
- W2069894028 cites W2022609707 @default.
- W2069894028 cites W2022825972 @default.
- W2069894028 cites W2023962370 @default.
- W2069894028 cites W2024395506 @default.
- W2069894028 cites W2032919364 @default.
- W2069894028 cites W2050161506 @default.
- W2069894028 cites W2066555189 @default.
- W2069894028 cites W2068817758 @default.
- W2069894028 cites W2070510406 @default.
- W2069894028 cites W2073002198 @default.
- W2069894028 cites W2074431333 @default.
- W2069894028 cites W2078290510 @default.
- W2069894028 cites W2086619421 @default.
- W2069894028 cites W2090196923 @default.
- W2069894028 cites W2098597355 @default.
- W2069894028 cites W2099448375 @default.
- W2069894028 cites W2101357408 @default.
- W2069894028 cites W2110094217 @default.
- W2069894028 cites W2110374888 @default.
- W2069894028 cites W2113435725 @default.
- W2069894028 cites W2114327599 @default.
- W2069894028 cites W2115807273 @default.
- W2069894028 cites W2116058450 @default.
- W2069894028 cites W2117787632 @default.
- W2069894028 cites W2120195741 @default.
- W2069894028 cites W2123194540 @default.
- W2069894028 cites W2127205775 @default.
- W2069894028 cites W2130842427 @default.
- W2069894028 cites W2131760639 @default.
- W2069894028 cites W2132297623 @default.
- W2069894028 cites W2149947428 @default.
- W2069894028 cites W2153253565 @default.
- W2069894028 cites W2161527093 @default.
- W2069894028 cites W2161641617 @default.
- W2069894028 cites W2166092131 @default.
- W2069894028 cites W2166328287 @default.
- W2069894028 cites W2170090311 @default.
- W2069894028 cites W4211174138 @default.
- W2069894028 cites W89295468 @default.
- W2069894028 doi "https://doi.org/10.1038/mp.2014.172" @default.
- W2069894028 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4653611" @default.
- W2069894028 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25560758" @default.
- W2069894028 hasPublicationYear "2015" @default.
- W2069894028 type Work @default.
- W2069894028 sameAs 2069894028 @default.
- W2069894028 citedByCount "63" @default.
- W2069894028 countsByYear W20698940282015 @default.
- W2069894028 countsByYear W20698940282016 @default.
- W2069894028 countsByYear W20698940282017 @default.
- W2069894028 countsByYear W20698940282018 @default.
- W2069894028 countsByYear W20698940282019 @default.
- W2069894028 countsByYear W20698940282020 @default.
- W2069894028 countsByYear W20698940282021 @default.
- W2069894028 countsByYear W20698940282022 @default.
- W2069894028 countsByYear W20698940282023 @default.
- W2069894028 crossrefType "journal-article" @default.
- W2069894028 hasAuthorship W2069894028A5008405084 @default.