Publication
Title
Homozygous and heterozygous disruptions of ANK3 : at the crossroads of neurodevelopmental and psychiatric disorders
Author
Abstract
AnkyrinG, encoded by the ANK3 gene, is involved in neuronal development and signaling. It has previously been implicated in bipolar disorder and schizophrenia by association studies. Most recently, de novo missense mutations in this gene were identified in autistic patients. However, the causative nature of these mutations remained controversial. Here, we report inactivating mutations in the Ankyrin 3 (ANK3) gene in patients with severe cognitive deficits. In a patient with a borderline intelligence, severe attention deficit hyperactivity disorder (ADHD), autism and sleeping problems, all isoforms of the ANK3 gene, were disrupted by a balanced translocation. Furthermore, in a consanguineous family with moderate intellectual disability (ID), an ADHD-like phenotype and behavioral problems, we identified a homozygous truncating frameshift mutation in the longest isoform of the same gene, which represents the first reported familial mutation in the ANK3 gene. The causality of ANK3 mutations in the two families and the role of the gene in cognitive function were supported by memory defects in a Drosophila knockdown model. Thus we demonstrated that ANK3 plays a role in intellectual functioning. In addition, our findings support the suggested association of ANK3 with various neuropsychiatric disorders and illustrate the genetic and molecular relation between a wide range of neurodevelopmental disorders.
Language
English
Source (journal)
Human molecular genetics. - Oxford
Publication
Oxford : 2013
ISSN
0964-6906
Volume/pages
22:10(2013), p. 1960-1970
ISI
000318559000005
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
GENCODYS: Genetic and Epigenetic Networks in Cognitive Dysfunction
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.04.2013
Last edited 19.08.2017
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