{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:22:27Z","timestamp":1780471347865,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Grange syndrome (GRNG\u2014MIM#135580) is a rare recessive disorder associating variable features including diffuse vascular stenosis, brachysyndactyly, osteopenia with increased bone fragility, cardiac malformations, and variable developmental delay. Since its first description in 1998, only 15 individuals from 10 families have been reported, carrying homozygous or compound heterozygous frameshift or nonsense variants in <jats:italic>YY1AP1<\/jats:italic>. In a patient with cutaneous and bone syndactyly and a hemorrhagic stroke at the age of 16\u2009months, consistent with a clinical diagnosis of GRNG, we performed exome sequencing after negative array\u2010CGH and congenital limb malformation panel results. Copy number variant analysis from exome data identified a homozygous intragenic out\u2010of\u2010frame deletion of 1.84\u2009kb encompassing exons seven and eight of <jats:italic>YY1AP1,<\/jats:italic> confirming a molecular diagnosis of GRNG. Genetic counseling led to the identification of additional family members compatible with GRNG. Here, we provide new insights into the phenotypic variability associated with GRNG and highlight the utility of the detection of small copy number variants to identify the molecular causes of heterogeneous malformative genetic disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.63394","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T11:20:50Z","timestamp":1694517650000},"page":"2728-2735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of the first homozygous intragenic deletion in the <scp>YY1AP1<\/scp> gene in a consanguineous family: New insights into the phenotypic variability associated with Grange syndrome"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-9204","authenticated-orcid":false,"given":"E.","family":"Viora\u2010Dupont","sequence":"first","affiliation":[{"name":"Genetics Department and Reference Center for Developmental Disorders and Malformative Syndromes for East France Dijon Bourgogne University Hospital  Dijon France"},{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8986-8222","authenticated-orcid":false,"given":"A.","family":"Denomm\u00e9\u2010Pichon","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Chevarin","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Patat","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Toulouse, France  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-0935","authenticated-orcid":false,"given":"M.","family":"Willems","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale Maladies Rares et M\u00e9decine Personnalis\u00e9e, Universit\u00e9 de Montpellier, CHU de Montpellier, CLAD ASOOR Montpellier  Montpellier France"},{"name":"Institute for Neurosciences of Montpellier Universit\u00e9 de Montpellier, INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Bourgon","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bruel","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Aubert\u2010Mucca","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Toulouse, France  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Galinier","sequence":"additional","affiliation":[{"name":"F\u00e9d\u00e9ration des Services de Cardiologie CHU Toulouse\u2010Rangueil  Toulouse France"},{"name":"UMR UT3 CNRS 5288 Evolutionary Medicine, Obesity and Heart Failure: Molecular and Clinical Investigations INI\u2010CRCT F\u2010CRIN, GREAT Networks  Toulouse France"},{"name":"Universit\u00e9 Paul Sabatier\u2010Toulouse III Facult\u00e9 de M\u00e9decine  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Itier","sequence":"additional","affiliation":[{"name":"UMR UT3 CNRS 5288 Evolutionary Medicine, Obesity and Heart Failure: Molecular and Clinical Investigations INI\u2010CRCT F\u2010CRIN, GREAT Networks  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Decramer","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Toulouse, Service de Nephrologie Pediatrique Hopital des Enfants, Centre De Reference des Maladies R\u00e9nales Rares du Sud\u2010Ouest  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Piton","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Gerard","sequence":"additional","affiliation":[{"name":"Laboratoire de Diagnostic G\u00e9n\u00e9tique, Institut de G\u00e9n\u00e9tique M\u00e9dicale d'Alsace H\u00f4pitaux Universitaires de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Billon","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares et D\u00e9partement de g\u00e9n\u00e9tique H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Jeunemaitre","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares et D\u00e9partement de g\u00e9n\u00e9tique H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Duffourd","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Callier","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Thauvin","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"},{"name":"Centre de R\u00e9f\u00e9rence D\u00e9ficiences Intellectuelles de Causes Rares H\u00f4pital d'Enfants  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Philippe","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-444X","authenticated-orcid":false,"given":"L.","family":"Faivre","sequence":"additional","affiliation":[{"name":"Genetics Department and Reference Center for Developmental Disorders and Malformative Syndromes for East France Dijon Bourgogne University Hospital  Dijon France"},{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Albuisson","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies Vasculaires Rares et D\u00e9partement de g\u00e9n\u00e9tique H\u00f4pital Europ\u00e9en Georges Pompidou  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-8374","authenticated-orcid":false,"given":"A.","family":"Vitobello","sequence":"additional","affiliation":[{"name":"UMR1231 GAD \u201cG\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement\u201d FHU\u2010TRANSLAD, UFR des Sciences de Sant\u00e9, INSERM\u2010University of Burgundy  Dijon France"},{"name":"Unit\u00e9 Fonctionnelle d'Innovation diagnostique des maladies rares Dijon Bourgogne University Hospital  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-00755-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.10819"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61379"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X18821816"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(19980217)75:5<469::aid-ajmg4>3.0.co;2-i"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.11.008"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527785"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.162"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15349"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-021-00328-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.60700"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0626-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12732"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12459"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35593"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31125"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310532200"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(2001)9999:9999<::AID-AJMG1138>3.0.CO;2-R"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T06:12:04Z","timestamp":1697263924000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/ajmg.a.63394"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63394","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]},"assertion":[{"value":"2023-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}