ArticleBiological psychiatry2009
Autism-associated haplotype affects the regulation of the homeobox gene, ENGRAILED 2.
Article in Biological psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
40 citing papers in PubMed, 82 citations in OpenAlex.
- Lcn2 deficiency leads to long-lasting social impairments independent of maternal immune activation.Journal of neuroinflammation · 2026Article
- Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways.Neurology international · 2025Review
- Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- A comprehensive review of GABA in autism spectrum disorders: associations, mechanisms, and therapeutic implications.Frontiers in psychiatry · 2025Review
- Engrailed-2 and inflammation convergently and independently impinge on cerebellar Purkinje cell differentiation.Journal of neuroinflammation · 2024Article
- Glial cells are affected more than interneurons by the loss of Engrailed 2 gene in the mouse cerebellum.Journal of anatomy · 2024Article
- Exploring the epigenetic landscape: The role of 5-hydroxymethylcytosine in neurodevelopmental disorders.Cambridge prisms. Precision medicine · 2024Review
- Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism.Molecular autism · 2023Article
- Implication of Hippocampal Neurogenesis in Autism Spectrum Disorder: Pathogenesis and Therapeutic Implications.Current neuropharmacology · 2023Review
- Review
- Abnormal Cerebellar Development in Autism Spectrum Disorders.Developmental neuroscience · 2021Review
- GABAergic System Dysfunction in Autism Spectrum Disorders.Frontiers in cell and developmental biology · 2021Review
- Molecules, Mechanisms, and Disorders of Self-Domestication: Keys for Understanding Emotional and Social Communication from an Evolutionary Perspective.Biomolecules · 2020Review
- Morphological alterations of the reticular thalamic nucleus in Engrailed-2 knockout mice.Journal of anatomy · 2020Article
- Article
- Aberrant Somatosensory Processing and Connectivity in Mice LackingThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Functional Outcomes of Cerebellar Malformations.Frontiers in cellular neuroscience · 2019Review
- Altered salt taste response and increased tongue epithelium Scnna1 expression in adult Engrailed-2 null mice.Physiology & behavior · 2018Article
- Clinical Phenotypes Associated to Engrailed 2 Gene Alterations in a Series of Neuropediatric Patients.Frontiers in neuroanatomy · 2018Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAssociation analysis identified the homeobox transcription factor, ENGRAILED 2 (EN2), as a possible autism spectrum disorder (ASD) susceptibility gene (ASD [MIM 608636]; EN2 [MIM 131310]). The common alleles (underlined) of two intronic single nucleotide polymorphisms (SNPs), rs1861972 (A/G) and rs1861973 (C/T), are over-transmitted to affected individuals both singly and as a haplotype in three separate datasets (518 families total, haplotype p = .00000035).
methodsFurther support that EN2 is a possible ASD susceptibility gene requires the identification of a risk allele, a DNA variant that is consistently associated with ASD but is also functional. To identify possible risk alleles, additional association analysis and linkage disequilibrium (LD) mapping were performed. Candidate polymorphisms were then tested for functional differences by luciferase (Luc) reporter transfections and electrophoretic mobility shift assays (EMSAs).
resultsAssociation analysis of additional EN2 polymorphisms and LD mapping with Hapmap SNPs identified the rs1861972-rs1861973 haplotype as the most appropriate candidate to test for functional differences. Luciferase reporters for the two common rs1861972-rs1861973 haplotypes (A-C and G-T) were then transfected into human and rat cell lines as well as primary mouse neuronal cultures. In all cases the A-C haplotype resulted in a significant increase in Luc levels (p < .005). The EMSAs were then performed, and nuclear factors were bound specifically to the A and C alleles of both SNPs.
conclusionsThese data indicate that the A-C haplotype is functional and, together with the association and LD mapping results, supports EN2 as a likely ASD susceptibility gene and the A-C haplotype as a possible risk allele.
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Registered trials
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