{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:29Z","timestamp":1753861769753,"version":"3.41.2"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006451","name":"Hospices Civils de Lyon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006451","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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62\u2009Mb minimal critical region at 20q11.2, encompassing three genes <jats:italic>GDF5<\/jats:italic>, <jats:italic>EPB41L1<\/jats:italic>, and <jats:italic>SAMHD1<\/jats:italic>, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359\u2009kb at 20q11.2, containing six MIM genes, including two disease\u2010causing genes, <jats:italic>GDF5<\/jats:italic> and <jats:italic>CEP250<\/jats:italic>. The second critical region spans 706\u2009kb at 20q12, encompassing four MIM genes, including two disease\u2010causing genes, <jats:italic>MAFB<\/jats:italic> and <jats:italic>TOP1<\/jats:italic>. We propose <jats:italic>GDF5<\/jats:italic> to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize <jats:italic>TOP1<\/jats:italic> as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.<\/jats:p>","DOI":"10.1002\/ajmg.a.63580","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T10:09:02Z","timestamp":1711015742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0936-9547","authenticated-orcid":false,"given":"Souad","family":"Bensaid","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon, GHE, Service de G\u00e9n\u00e9tique  Lyon France"},{"name":"Laboratoire d'Environnement et de Sant\u00e9, Universit\u00e9 de Sidi Bel Abb\u00e9s, UDL  Sidi Bel Abb\u00e9s Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-2782","authenticated-orcid":false,"given":"Malika","family":"Bendahmane","sequence":"additional","affiliation":[{"name":"Laboratoire d'Environnement et de Sant\u00e9, Universit\u00e9 de Sidi Bel Abb\u00e9s, UDL  Sidi Bel Abb\u00e9s Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-3519","authenticated-orcid":false,"given":"Sara","family":"Loddo","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-4866","authenticated-orcid":false,"given":"Gemma","family":"Poke","sequence":"additional","affiliation":[{"name":"Genetic Health Service New Zealand, Wellington Hospital  Wellington New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1427-4153","authenticated-orcid":false,"given":"Louis","family":"Januel","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, GHE, Service de G\u00e9n\u00e9tique  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8578-9095","authenticated-orcid":false,"given":"Romain","family":"Nicolle","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pital Necker\u2010Enfants Malades, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique et M\u00e9decine G\u00e9nomique, Service de M\u00e9decine G\u00e9nomique des Maladies Rares  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-4958","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Malan","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pital Necker\u2010Enfants Malades, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique et M\u00e9decine G\u00e9nomique, Service de M\u00e9decine G\u00e9nomique des Maladies Rares  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-0981","authenticated-orcid":false,"given":"Nicolas","family":"Chatron","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, GHE, Service de G\u00e9n\u00e9tique  Lyon France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, CNRS, INSERM, Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, UMR5261, U1315, Institut NeuroMyoG\u00e8ne  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Ottombrino","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-5906","authenticated-orcid":false,"given":"Maria Lisa","family":"Dentici","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Bambino Ges\u00f9 Children Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Digilio","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Bambino Ges\u00f9 Children Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-2849","authenticated-orcid":false,"given":"Damien","family":"Sanlaville","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, GHE, Service de G\u00e9n\u00e9tique  Lyon France"},{"name":"Universit\u00e9 Claude Bernard Lyon 1, CNRS, INSERM, Physiopathologie et G\u00e9n\u00e9tique du Neurone et du Muscle, UMR5261, U1315, Institut NeuroMyoG\u00e8ne  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1016\/j.ejpn.2013.04.010"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1002\/ajmg.a.31395"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1016\/j.ydbio.2017.04.017"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1038\/nature07267"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1186\/1471-2350-14-41"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1038\/hgv.2017.50"},{"issue":"11","key":"e_1_2_10_8_1","first-page":"573","article-title":"Membrane\u2010type 5 matrix metalloproteinase is expressed in differentiated neurons and regulates axonal growth","volume":"12","author":"Hayashita\u2010Kinoh H.","year":"2001","journal-title":"Cell Growth & Differentiation: The Molecular Biology Journal of the American Association for Cancer Research"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1002\/ajmg.a.33818"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.1371\/journal.pone.0262488"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1155\/2013\/353028"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1002\/ajmg.a.31844"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1002\/ajmg.a.36882"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.53738\/REVMED.2018.14.619.1666"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1038\/s41598-019-57011-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1038\/nature12504"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1002\/ajmg.a.61758"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1016\/j.jpurol.2020.10.006"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1159\/000493935"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1006\/dbio.1998.9129"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1038\/nature11011"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1242\/dev.101378"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1016\/j.ajhg.2016.03.023"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.1136\/jmg.24.2.93"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1002\/ajmg.a.36394"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1097\/MCD.0b013e32835b8ea4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1136\/jmg.30.2.171"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1242\/dev.122.12.3969"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.1002\/dvdy.399"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1038\/nrm831"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1006\/geno.1999.5884"}],"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.63580","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T15:29:45Z","timestamp":1717774185000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/ajmg.a.63580"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63580","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,3,21]]},"assertion":[{"value":"2023-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63580"}}