ArticleJournal of psychiatry & neuroscience : JPN2019
Truncating variant burden in high-functioning autism and pleiotropic effects of LRP1 across psychiatric phenotypes
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Article in Journal of psychiatry & neuroscience : JPN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Heterozygous Variants in LRP1 Cause a Neurodevelopmental Disorder With Congenital Heart Defects.American journal of medical genetics. Part A · 2026Article
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- mMolecular neurobiology · 2026Article
- Gene editing in "cell villages" enables exploring disease-relevant mutations in many genetic backgrounds.bioRxiv : the preprint server for biology · 2025Article
- Advancing precision diagnosis in autism: Insights from large-scale genomic studies.Molecules and cells · 2025Review
- Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.American journal of human genetics · 2025Article
- Astrocytic-supplied cholesterol drives synaptic gene expression programs in developing neurons and downstream astrocytic transcriptional programs.bioRxiv : the preprint server for biology · 2025Article
- Dysfunction of cAMP-Protein Kinase A-Calcium Signaling Axis in Striatal Medium Spiny Neurons: A Role in Schizophrenia and Huntington's Disease Neuropathology.Biological psychiatry global open science · 2023Article
- Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review.Nutrients · 2023Review
- Prediction Model for Sensory Perception Abnormality in Autism Spectrum Disorder.International journal of molecular sciences · 2023Article
- Low-density lipoprotein receptor-related protein-1 (LRP1) in the glial lineage modulates neuronal excitability.Frontiers in network physiology · 2023Review
- CaFrontiers in cell and developmental biology · 2023Article
- A linkage and exome study of multiplex families with bipolar disorder implicates rare coding variants of ANK3 and additional rare alleles at 10q11-q21.Journal of psychiatry & neuroscience : JPN · 2021Article
- A Review of Genetic and Physiological Disease Mechanisms Associated With Cav1 Channels: Implications for Incomplete Congenital Stationary Night Blindness Treatment.Frontiers in genetics · 2021Article
- Identifying Subgroups of Patients With Autism by Gene Expression Profiles Using Machine Learning Algorithms.Frontiers in psychiatry · 2021Article
- The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia.Complex psychiatry · 2020Review
- Involvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analyses.Journal of clinical medicine · 2020Article
- De Novo Gene Variants and Familial Bipolar Disorder.JAMA network open · 2020Article
- The rs594445 in MOCOS gene is associated with risk of autism spectrum disorder.Metabolic brain disease · 2020Article
- Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome.International journal of molecular sciences · 2019Review
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Authors and funding
11 authors at 7 institutions in 2 countries.
Bàrbara TorricoFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Alex D. ShawFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Roberto MoscaFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Norma Vivó-LuqueFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Amaia HervásFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Noèlia Fernàndez-CastilloFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Patrick AloyFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Mònica BayésFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Janice M. FullertonFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Bru CormandFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Claudio TomaFrom the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain (Torrico, Vivó-Luque, Fernàndez-Castillo, Cormand, Toma); the Institute of Biomedicine, University of Barcelona, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand, Toma); the Institut de Recerca Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain (Torrico, Fernàndez-Castillo, Cormand); the Neuroscience Research Australia, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia (Shaw, Fullerton, Toma); the Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain (Mosca, Aloy); the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain (Hervás); the Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (Aloy); and the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain (Bayés).
Institute for Research in Biomedicine · ESCentro Nacional de Análisis Genómico · ESCentre for Biomedical Network Research on Rare Diseases · ESHospital Sant Joan de Déu Barcelona · ESInstitució Catalana de Recerca i Estudis Avançats · ESMútua Terrassa · ESUniversitat de Barcelona · ES
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
AdolescentAdultAllelesAutism Spectrum DisorderAutistic DisorderDatabases, GeneticEpilepsyExome SequencingFamilyFemaleGene Regulatory NetworksGenetic PleiotropyHumansIntellectual DisabilityLow Density Lipoprotein Receptor-Related Protein-1MaleLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, human
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