CNTNAP2 is significantly associated with schizophrenia and major depression in the Han Chinese population

Ji, Weidong; Li, Tao; Pan, Yaosheng; Tao, Hua; Ju, Kang; Wen, Zujia; Fu, Yingchun; An, Zhiguo; Zhao, Qian; Wang, Ti; He, Lin; Gao, Feng; Quan, Yi; Shi, Yongyong

doi:10.1016/j.psychres.2012.09.024

Cited by 56 publications

(39 citation statements)

References 16 publications

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“…CNTNAP2 variants are associated with complex disorders Genome-wide association studies have also linked CNTNAP2 to complex neurological disorders, including language impairment, autism, dyslexia, schizophrenia, and depression 18,20,[22][23][24][25][26] (Table 2), although causal variants have not yet been identified. Convincing evidence has linked common variants (ie, single nucleotide polymorphisms; SNPs) in the CNTNAP2 region with the most common form of language disorder in children: specific language impairment (SLI).…”

Section: Cntnap2 and Cognitive Disorders Mutations Of Cntnap2mentioning

confidence: 99%

Shining a light on CNTNAP2: complex functions to complex disorders

2013

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The genetic basis of complex neurological disorders involving language are poorly understood, partly due to the multiple additive genetic risk factors that are thought to be responsible. Furthermore, these conditions are often syndromic in that they have a range of endophenotypes that may be associated with the disorder and that may be present in different combinations in patients. However, the emergence of individual genes implicated across multiple disorders has suggested that they might share similar underlying genetic mechanisms. The CNTNAP2 gene is an excellent example of this, as it has recently been implicated in a broad range of phenotypes including autism spectrum disorder (ASD), schizophrenia, intellectual disability, dyslexia and language impairment. This review considers the evidence implicating CNTNAP2 in these conditions, the genetic risk factors and mutations that have been identified in patient and population studies and how these relate to patient phenotypes. The role of CNTNAP2 is examined in the context of larger neurogenetic networks during development and disorder, given what is known regarding the regulation and function of this gene. Understanding the role of CNTNAP2 in diverse neurological disorders will further our understanding of how combinations of individual genetic risk factors can contribute to complex conditions.

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Section: Cntnap2 and Cognitive Disorders Mutations Of Cntnap2mentioning

confidence: 99%

Shining a light on CNTNAP2: complex functions to complex disorders

2013

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“…In the Chinese Han population, CNTNAP2 associates with schizophrenia and major depression [Ji et al, 2013]. In 2 patients with schizophrenia and seizures from 2 independent families with multiple psychiatric disorders, heterozygous deletions of part of CNTNAP2 were transmitted from healthy parents ( Fig.…”

Section: The Phenotypic Scope Of Cntnap2 Deletion Disordersmentioning

confidence: 99%

Intragenic CNTNAP2 Deletions: A Bridge Too Far

Poot¹

2017

Mol Syndromol

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Intragenic deletions of the contactin-associated protein-like 2 gene (CNTNAP2) have been found in patients with Gilles de la Tourette syndrome, intellectual disability (ID), obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, stuttering, and attention deficit hyperactivity disorder. A variety of molecular mechanisms, such as loss of transcription factor binding sites and perturbation of penetrance and expressivity, have been proposed to account for the phenotypic variability resulting from CNTNAP2 mutations. Deletions of both CNTNAP2 alleles produced truncated proteins lacking the transmembrane or some of the extracellular domains, or no protein at all. This observation can be extended to heterozygous intragenic deletions by assuming that such deletion-containing alleles lead to expression of a Caspr2 protein lacking one or several extracellular domains. Such altered forms of Capr2 proteins will lack the ability to bridge the intercellular space between neurons by binding to partners, such as CNTN1, CNTN2, DLG1, and DLG4. This presumed effect of intragenic deletions of CNTNAP2, and possibly other genes involved in connecting neuronal cells, represents a molecular basis for the postulated neuronal hypoconnectivity in autism and probably other neurodevelopmental disorders, including epilepsy, ID, language impairments and schizophrenia. Thus, CNTNAP2 may represent a paradigmatic case of a gene functioning as a node in a genetic and cellular network governing brain development and acquisition of higher cognitive functions.

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“…3 ; table 1 ) [Alarcon et al, 2008;Arking et al, 2008;Newbury et al, 2011;Peter et al, 2011;Villanueva et al, 2011;Whitehouse et al, 2011;Anney et al, 2012;Ji et al, 2013;Sampath et al, 2013;Toma et al, 2013;Poot, 2014;Rodenas-Cuadrado et al, 2014].…”

Section: Association Of Cntnap2 With Neurodevelopmental Disordersunclassified

“…3 , green arrow). In addition, SNP rs2710102 associates with ASD and with major depression [Alarcon et al, 2008;Ji et al, 2013]. This may either reflect shared phenotypes or endophenotypes in these disorders [Rode- …”

Section: Association Of Cntnap2 With Neurodevelopmental Disordersmentioning

confidence: 99%

Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders

Poot¹

2015

Mol Syndromol

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Based on genomic rearrangements and copy number variations, the contactin-associated protein-like 2 gene (CNTNAP2) has been implicated in neurodevelopmental disorders such as Gilles de la Tourette syndrome, intellectual disability, obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, and attention deficit hyperactivity disorder. To explain the phenotypic pleiotropy of CNTNAP2 alterations, several hypotheses have been put forward. Those include gene disruption, loss of a gene copy by a heterozygous deletion, altered regulation of gene expression due to loss of transcription factor binding and DNA methylation sites, and mutations in the amino acid sequence of the encoded protein which may provoke altered interactions of the CNTNAP2-encoded protein, Caspr2, with other proteins. Also exome sequencing, which covers <0.2% of the CNTNAP2 genomic DNA, has revealed numerous single nucleotide variants in healthy individuals and in patients with neurodevelopmental disorders. In some of these disorders, disruption of CNTNAP2 may be interpreted as a susceptibility factor rather than a directly causative mutation. In addition to being associated with impaired development of language, CNTNAP2 may turn out to be a central node in the molecular networks controlling neurodevelopment. This review discusses the impact of CNTNAP2 mutations on its functioning at multiple levels of the combinatorial genetic networks that govern brain development. In addition, recommendations for genomic testing in the context of clinical genetic management of patients with neurodevelopmental disorders and their families are put forward.

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CNTNAP2 is significantly associated with schizophrenia and major depression in the Han Chinese population

Cited by 56 publications

References 16 publications

Shining a light on CNTNAP2: complex functions to complex disorders

Shining a light on CNTNAP2: complex functions to complex disorders

Intragenic CNTNAP2 Deletions: A Bridge Too Far

Connecting the CNTNAP2 Networks with Neurodevelopmental Disorders

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