{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:17Z","timestamp":1772160077014,"version":"3.50.1"},"reference-count":14,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>CTNND2<\/jats:italic>\n                    encodes \u03b4\u2010catenin, a component of an adherens junction complex, and plays an important role in neuronal structure and function. To date, only heterozygous loss\u2010of\u2010function\n                    <jats:italic>CTNND2<\/jats:italic>\n                    variants have been associated with mild neurodevelopmental delay and behavioral anomalies, a condition, which we named Rauch\u2010Azzarello syndrome. Here, we report three siblings of a consanguineous family of Syrian descent with a homozygous deletion encompassing the last 19 exons of\n                    <jats:italic>CTNND2<\/jats:italic>\n                    predicted to disrupt the transcript. All presented with severe neurodevelopmental delay with absent speech, profound motor delay, stereotypic behavior, microcephaly, short stature, muscular hypotonia with lower limb hypertonia, and variable eye anomalies. The parents and the fourth sibling were heterozygous carriers of the deletion and exhibited mild neurodevelopmental impairment resembling that of the previously described heterozygous individuals. The present study unveils a severe manifestation of\n                    <jats:italic>CTNND2<\/jats:italic>\n                    \u2010associated Rauch\u2010Azzarello syndrome attributed to biallelic loss\u2010of\u2010function aberrations, clinically distinct from the already described mild presentation of heterozygous individuals. Furthermore, we demonstrate novel clinical features in homozygous individuals that have not been reported in heterozygous cases to date.\n                  <\/jats:p>","DOI":"10.1111\/cge.14532","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T21:29:00Z","timestamp":1712870940000},"page":"180-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Severe manifestation of\n                    <scp>Rauch\u2010Azzarello<\/scp>\n                    syndrome associated with biallelic deletion of\n                    <scp>\n                      <i>CTNND2<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"106","author":[{"given":"Melissa","family":"Pauly","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy","family":"Krumbiegel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Trumpp","sequence":"additional","affiliation":[{"name":"Children's Clinic Klinikum Bayreuth GmbH  Bayreuth Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Braig","sequence":"additional","affiliation":[{"name":"Children's Clinic Klinikum Bayreuth GmbH  Bayreuth Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Rupprecht","sequence":"additional","affiliation":[{"name":"Children's Clinic Klinikum Bayreuth GmbH  Bayreuth Germany"},{"name":"MCO Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Kraus","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffen","family":"Uebe","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Centre for Rare Diseases Erlangen (ZSEER) Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia","family":"Vasileiou","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"},{"name":"Centre for Rare Diseases Erlangen (ZSEER) Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199705260-00054"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4534"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102757"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1205653"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.09.026"},{"issue":"1","key":"e_1_2_11_7_1","article-title":"Disruption of CTNND2, encoding delta\u2010catenin, causes a penetrant attention deficit disorder and myopia","volume":"1","author":"Adegbola A","year":"2020","journal-title":"HGG 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