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http://hdl.handle.net/2445/149618
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DC Field | Value | Language |
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dc.contributor.author | Torrico Avilés, Bàrbara | - |
dc.contributor.author | Shaw, Alex D. | - |
dc.contributor.author | Mosca, Roberto | - |
dc.contributor.author | Vivó-Luque, Norma | - |
dc.contributor.author | Hervás, A. | - |
dc.contributor.author | Fernàndez Castillo, Noèlia | - |
dc.contributor.author | Aloy, Patrick, 1972- | - |
dc.contributor.author | Bayés Colomer, Mònica | - |
dc.contributor.author | Fullerton, J.M. | - |
dc.contributor.author | Cormand Rifà, Bru | - |
dc.contributor.author | Toma, Claudio | - |
dc.date.accessioned | 2020-02-07T15:08:34Z | - |
dc.date.available | 2020-02-07T15:08:34Z | - |
dc.date.issued | 2019-05-16 | - |
dc.identifier.issn | 1180-4882 | - |
dc.identifier.uri | http://hdl.handle.net/2445/149618 | - |
dc.description.abstract | Background: Previous research has implicated de novo and inherited truncating mutations in autism-spectrum disorder. We aim to investigate whether the load of inherited truncating mutations contributes similarly to high-functioning autism, and to characterize genes that harbour de novo variants in high-functioning autism. Methods: We performed whole-exome sequencing in 20 high-functioning autism families (average IQ = 100). Results: We observed no difference in the number of transmitted versus nontransmitted truncating alleles for high-functioning autism (117 v. 130, p = 0.78). Transmitted truncating and de novo variants in high-functioning autism were not enriched in gene ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG) categories, or in autism-related gene sets. However, in a patient with high-functioning autism we identified a de novo variant in a canonical splice site of LRP1, a postsynaptic density gene that is a target for fragile X mental retardation protein (FRMP). This de novo variant leads to in-frame skipping of exon 29, removing 2 of 6 blades of the β-propeller domain 4 of LRP1, with putative functional consequences. Large data sets implicate LRP1 across a number of psychiatric disorders: de novo variants are associated with autism-spectrum disorder (p = 0.039) and schizophrenia (p = 0.008) from combined sequencing projects; common variants using genome-wide association study data sets from the Psychiatric Genomics Consortium show gene-based association in schizophrenia (p = 6.6 × E−07) and in a meta-analysis across 7 psychiatric disorders (p = 2.3 × E−03); and the burden of ultra-rare pathogenic variants has been shown to be higher in autism-spectrum disorder (p = 1.2 × E−05), using whole-exome sequencing from 6135 patients with schizophrenia, 1778 patients with autism-spectrum disorder and 7875 controls. Limitations: We had a limited sample of patients with high-functioning autism, related to difficulty in recruiting probands with high cognitive performance and no family history of psychiatric disorders. Conclusion: Previous studies and ours suggest an effect of truncating mutations restricted to severe autism-spectrum disorder phenotypes that are associated with intellectual disability. We provide evidence for pleiotropic effects of common and rare variants in the LRP1 gene across psychiatric phenotypes. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Canadian Medical Association | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1503/jpn.180184 | - |
dc.relation.ispartof | Journal of Psychiatry & Neuroscience, 2019, vol. 44, num. 5, p. 350-359 | - |
dc.relation.uri | https://doi.org/10.1503/jpn.180184 | - |
dc.rights | (c) Torrico Avilés, Bàrbara et al., 2019 | - |
dc.source | Articles publicats en revistes (Genètica, Microbiologia i Estadística) | - |
dc.subject.classification | Autisme | - |
dc.subject.other | Autism | - |
dc.title | Truncating variant burden in high functioning autism and pleiotropic effects of lrp1 across psychiatric phenotypes | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 685746 | - |
dc.date.updated | 2020-02-07T15:08:34Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/667302/EU//CoCA | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31094488 | - |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
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685746.pdf | 662.36 kB | Adobe PDF | View/Open |
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