Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia

Abidemi Adegbola; Richard Lutz; Elina Nikkola; Samuel P. Strom; Jonathan Picker; Anthony Wynshaw-Boris

doi:10.1016/j.xhgg.2020.100007

Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia

Abidemi Adegbola, Richard Lutz, Elina Nikkola, Samuel P. Strom, Jonathan Picker, Anthony Wynshaw-Boris

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts CTNND2 in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. CTNND2 encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders. Therefore, we propose that the severe and highly penetrant nature of the ADHD phenotype in affected individuals identifies CTNND2 as a potential gateway to ADHD pathophysiology similar to the DISC1 translocation in psychosis or AUTS2 in autism.

Original language	English (US)
Article number	100007
Journal	Human Genetics and Genomics Advances
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.xhgg.2020.100007
State	Published - Oct 22 2020

Keywords

Nanopore sequencing
attention deficit hyperactivity disorder (ADHD)
familial ADHD
gene identification
myopia
neurodevelopment
protein-truncating variants (PTVs)
refractive error of the eye
translocation mapping
whole genome sequencing

ASJC Scopus subject areas

Molecular Medicine
Genetics(clinical)

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10.1016/j.xhgg.2020.100007

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title = "Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia",

abstract = "Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts CTNND2 in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. CTNND2 encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders. Therefore, we propose that the severe and highly penetrant nature of the ADHD phenotype in affected individuals identifies CTNND2 as a potential gateway to ADHD pathophysiology similar to the DISC1 translocation in psychosis or AUTS2 in autism.",

keywords = "Nanopore sequencing, attention deficit hyperactivity disorder (ADHD), familial ADHD, gene identification, myopia, neurodevelopment, protein-truncating variants (PTVs), refractive error of the eye, translocation mapping, whole genome sequencing",

author = "Abidemi Adegbola and Richard Lutz and Elina Nikkola and Strom, {Samuel P.} and Jonathan Picker and Anthony Wynshaw-Boris",

note = "Funding Information: We thank Dr. Neil Molyneaux and Dr. Alexander Miron (Case Western Reserve University) for bioinformatics assistance. We thank Mirandy Teguh (Fulgent Genetics) for custom qPCR work and Jessa Humanski (Fulgent Genetics) for coordination. This publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, 4UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research (A.A) and the US National Institutes of Health (R01MH113106; A.W.-B.). Publisher Copyright: {\textcopyright} 2020 The Authors",

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AU - Adegbola, Abidemi

AU - Lutz, Richard

AU - Nikkola, Elina

AU - Strom, Samuel P.

AU - Picker, Jonathan

AU - Wynshaw-Boris, Anthony

N1 - Funding Information: We thank Dr. Neil Molyneaux and Dr. Alexander Miron (Case Western Reserve University) for bioinformatics assistance. We thank Mirandy Teguh (Fulgent Genetics) for custom qPCR work and Jessa Humanski (Fulgent Genetics) for coordination. This publication was made possible by the Clinical and Translational Science Collaborative of Cleveland, 4UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research (A.A) and the US National Institutes of Health (R01MH113106; A.W.-B.). Publisher Copyright: © 2020 The Authors

PY - 2020/10/22

Y1 - 2020/10/22

N2 - Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts CTNND2 in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. CTNND2 encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders. Therefore, we propose that the severe and highly penetrant nature of the ADHD phenotype in affected individuals identifies CTNND2 as a potential gateway to ADHD pathophysiology similar to the DISC1 translocation in psychosis or AUTS2 in autism.

AB - Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with poorly understood pathophysiology and genetic mechanisms. A balanced chromosomal translocation interrupts CTNND2 in several members of a family with profound attentional deficit and myopia, and disruption of the gene was found in a separate unrelated individual with ADHD and myopia. CTNND2 encodes a brain-specific member of the adherens junction complex essential for postsynaptic and dendritic development, a site of potential pathophysiology in attentional disorders. Therefore, we propose that the severe and highly penetrant nature of the ADHD phenotype in affected individuals identifies CTNND2 as a potential gateway to ADHD pathophysiology similar to the DISC1 translocation in psychosis or AUTS2 in autism.

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Disruption of CTNND2, encoding delta-catenin, causes a penetrant attention deficit disorder and myopia

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