Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder.
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| Title: | Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder. |
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| Authors: | Gharani, N., Benayed, R., Mancuso, V., Brzustowicz, L. M., Millonig, J. H. |
| Source: | Molecular Psychiatry. May2004, Vol. 9 Issue 5, p474-484. 11p. |
| Subjects: | Homeobox genes, Genes, Autism, Developmental disabilities, Cerebellum diseases, Genetic polymorphisms |
| Abstract: | Mouse mutants of the homeobox transcription factor Engrailed2 (En2) and autistic individuals display similar cerebellar morphological abnormalities, which include hypoplasia and a decrease in the number of Purkinje cells.1–19 Human EN2 maps to 7q36, a chromosomal region that has demonstrated suggestive linkage to autism spectrum disorder (ASD).20–22 To investigate EN2 for evidence of association with ASD, four single-nucleotide polymorphisms (SNPs) (rs3735653, rs1861972, rs1861973, rs2361689) that span the majority of the 8.0 kb gene were assessed by the transmission/disequilibrium test23–26. Initially, 138 triads of autistic individuals and their parents were tested. Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005). Flanking exonic SNPs (rs3735653 and rs2361689) did not display association. This analysis was then extended to include 167 small nuclear ASD pedigrees and significant association was again only observed for rs1861972 and rs1861973 under both the narrow and broad diagnostic criteria (narrow: rs1861972 P=0.0290, rs1861973 P=0.0073, haplotype P=0.0009; broad: rs1861972 P=0.0175, rs1861973 P=0.0107, haplotype P=0.0024). These data demonstrate association between a cerebellar patterning gene and ASD, suggesting a role for EN2 as a susceptibility locus and supporting a neurodevelopmental defect hypothesis in the etiology of autism. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 13009034 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Gharani%2C+N%2E%22">Gharani, N.</searchLink><br /><searchLink fieldCode="AR" term="%22Benayed%2C+R%2E%22">Benayed, R.</searchLink><br /><searchLink fieldCode="AR" term="%22Mancuso%2C+V%2E%22">Mancuso, V.</searchLink><br /><searchLink fieldCode="AR" term="%22Brzustowicz%2C+L%2E+M%2E%22">Brzustowicz, L. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Millonig%2C+J%2E+H%2E%22">Millonig, J. H.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. May2004, Vol. 9 Issue 5, p474-484. 11p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Homeobox+genes%22">Homeobox genes</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Autism%22">Autism</searchLink><br /><searchLink fieldCode="DE" term="%22Developmental+disabilities%22">Developmental disabilities</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebellum+diseases%22">Cerebellum diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Mouse mutants of the homeobox transcription factor Engrailed2 (En2) and autistic individuals display similar cerebellar morphological abnormalities, which include hypoplasia and a decrease in the number of Purkinje cells.1–19 Human EN2 maps to 7q36, a chromosomal region that has demonstrated suggestive linkage to autism spectrum disorder (ASD).20–22 To investigate EN2 for evidence of association with ASD, four single-nucleotide polymorphisms (SNPs) (rs3735653, rs1861972, rs1861973, rs2361689) that span the majority of the 8.0 kb gene were assessed by the transmission/disequilibrium test23–26. Initially, 138 triads of autistic individuals and their parents were tested. Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005). Flanking exonic SNPs (rs3735653 and rs2361689) did not display association. This analysis was then extended to include 167 small nuclear ASD pedigrees and significant association was again only observed for rs1861972 and rs1861973 under both the narrow and broad diagnostic criteria (narrow: rs1861972 P=0.0290, rs1861973 P=0.0073, haplotype P=0.0009; broad: rs1861972 P=0.0175, rs1861973 P=0.0107, haplotype P=0.0024). These data demonstrate association between a cerebellar patterning gene and ASD, suggesting a role for EN2 as a susceptibility locus and supporting a neurodevelopmental defect hypothesis in the etiology of autism. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/sj.mp.4001498 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 474 Subjects: – SubjectFull: Homeobox genes Type: general – SubjectFull: Genes Type: general – SubjectFull: Autism Type: general – SubjectFull: Developmental disabilities Type: general – SubjectFull: Cerebellum diseases Type: general – SubjectFull: Genetic polymorphisms Type: general Titles: – TitleFull: Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Gharani, N. – PersonEntity: Name: NameFull: Benayed, R. – PersonEntity: Name: NameFull: Mancuso, V. – PersonEntity: Name: NameFull: Brzustowicz, L. M. – PersonEntity: Name: NameFull: Millonig, J. H. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2004 Type: published Y: 2004 Identifiers: – Type: issn-print Value: 13594184 Numbering: – Type: volume Value: 9 – Type: issue Value: 5 Titles: – TitleFull: Molecular Psychiatry Type: main |
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