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

6 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
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 - 22 Oct 2020
Externally published	Yes

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

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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",

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AU - Adegbola, Abidemi

AU - Lutz, Richard

AU - Nikkola, Elina

AU - Strom, Samuel P.

AU - Picker, Jonathan

AU - Wynshaw-Boris, Anthony

PY - 2020/10/22

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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.

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KW - Nanopore sequencing

KW - attention deficit hyperactivity disorder (ADHD)

KW - familial ADHD

KW - gene identification

KW - myopia

KW - neurodevelopment

KW - protein-truncating variants (PTVs)

KW - refractive error of the eye

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KW - whole genome sequencing

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

Abstract

Keywords

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