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Karger AG","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Based on genomic rearrangements and copy number variations, the contactin-associated protein-like 2 gene &lt;i&gt;(CNTNAP2)&lt;\/i&gt; 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 &lt;i&gt;CNTNAP2&lt;\/i&gt; 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 &lt;i&gt;CNTNAP2&lt;\/i&gt;-encoded protein, Caspr2, with other proteins. Also exome sequencing, which covers &lt;0.2% of the &lt;i&gt;CNTNAP2&lt;\/i&gt; genomic DNA, has revealed numerous single nucleotide variants in healthy individuals and in patients with neurodevelopmental disorders. In some of these disorders, disruption of &lt;i&gt;CNTNAP2&lt;\/i&gt; may be interpreted as a susceptibility factor rather than a directly causative mutation. In addition to being associated with impaired development of language, &lt;i&gt;CNTNAP2&lt;\/i&gt; may turn out to be a central node in the molecular networks controlling neurodevelopment. This review discusses the impact of &lt;i&gt;CNTNAP2&lt;\/i&gt; 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.<\/jats:p>","DOI":"10.1159\/000371594","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T07:25:15Z","timestamp":1422948315000},"page":"7-22","source":"Crossref","is-referenced-by-count":113,"title":["Connecting the CNTNAP2 Networks with Neurodevelopmental 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