{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:49:30Z","timestamp":1772992170212,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Marfanoid habitus and intellectual disability (MHID) co\u2010occur in multiple neurodevelopmental disorders (NDD). Among those, Lujan\u2010Fryns, an X\u2010linked genetic disorder associated with variants in\n                    <jats:italic>MED12<\/jats:italic>\n                    was the first such syndrome identified. Accurate molecular diagnosis for these MHID syndromes remains a challenge due to significant clinical and genetic heterogeneity. We present a case report of a 20\u2010year\u2010old male patient with MHID and severe social anxiety. A comprehensive clinical evaluation, including morphotype assessment, cognitive, and psychometric and genetic testing, was conducted to provide a detailed understanding of the patient's complex clinical presentation. Psychometric assessments revealed severe social anxiety and various cognitive and emotional challenges. Despite some autism\u2010like symptoms, the patient's clinical presentation was more aligned with mild intellectual disability. Exome sequencing was inconclusive but identified a heterozygous de novo missense variant in the\n                    <jats:italic>PCDHGA5<\/jats:italic>\n                    gene. This gene is not known in human pathology yet, but we also report a second patient with a syndromic neurodevelopmental disorder and a rare de novo variant which leads us to propose this as a candidate gene. Our findings emphasize the importance of multidisciplinary approach in the diagnosis and management of MHID. This case report underscores the need for objective clinical evaluations and standardized tools to better understand the complex clinical profiles of patients with NDDs. The identification of novel\n                    <jats:italic>PCDHGA5<\/jats:italic>\n                    gene variants adds this gene's candidacy to the genetic landscape of MHID\u2010NDD, warranting further investigation to determine its potential contribution.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.32087","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T08:35:21Z","timestamp":1712651721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigations of an individual with a Marfanoid habitus, mild intellectual disability, and severe social anxiety identifies\n                    <i>PCDHGA5<\/i>\n                    as a candidate neurodevelopmental disorder gene"],"prefix":"10.1002","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-0716","authenticated-orcid":false,"given":"Henri","family":"Margot","sequence":"first","affiliation":[{"name":"Univ. Bordeaux, MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1276-4246","authenticated-orcid":false,"given":"Adrien","family":"Pizano","sequence":"additional","affiliation":[{"name":"Aquitaine Autism Resources Centre, Centre Hospitalier Charles\u2010Perrens University Pole of Child and Adolescent Psychiatry  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6544-0152","authenticated-orcid":false,"given":"Anouck","family":"Amestoy","sequence":"additional","affiliation":[{"name":"Aquitaine Autism Resources Centre, Centre Hospitalier Charles\u2010Perrens University Pole of Child and Adolescent Psychiatry  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-2207","authenticated-orcid":false,"given":"Didier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-3689","authenticated-orcid":false,"given":"Camille","family":"Berges","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-523X","authenticated-orcid":false,"given":"Claire","family":"Beneteau","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, MRGM INSERM U1211, CHU de Bordeaux, Service de G\u00e9n\u00e9tique M\u00e9dicale  Bordeaux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-5467","authenticated-orcid":false,"given":"A. Micheil","family":"Innes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Pediatrics and Alberta Children's Hospital Research Institute University of Calgary  Calgary Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000220610.24908.a4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12094"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.162"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106425"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181bd3d90"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10144"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5812\/zjrms.64126"},{"key":"e_1_2_8_10_1","first-page":"241","article-title":"X\u2010linked mental retardation with Marfanoid habitus: A changing phenotype with age?","volume":"2","author":"Fryns J. 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