{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:16:53Z","timestamp":1790702213200,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,12,22]],"date-time":"2010-12-22T00:00:00Z","timestamp":1292976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>Zirn B, Arning L, Bartels I, Shoukier M, Hoffjan S, Neubauer B, Hahn A. Ring chromosome 22 and neurofibromatosis type II: proof of two\u2010hit model for the loss of the <jats:italic>NF2<\/jats:italic> gene in the development of meningioma.<\/jats:p><jats:p>Carriers of a ring chromosome 22 are mentally retarded and show variable facial dysmorphism. They may also present with features of neurofibromatosis type II (NF2) such as vestibular schwannomas and multiple meningiomas. In these cases, tumourigenesis has been suspected to be caused by the loss of both alleles of the <jats:italic>NF2<\/jats:italic> gene, a tumour suppressor localized in 22q12.2. Here, we describe an 18\u2010year\u2010old patient with constitutional ring chromosome 22 and mental retardation who developed rapid\u2010onset spastic paraparesis at the age of 15 years. The causative spinal meningioma at the level of T3, which compressed the spinal cord, was surgically removed, and the patient regained ambulation. Array comparative genomic hybridization (array CGH) and multiplex ligation\u2010dependent probe amplification (MLPA) analyses in blood revealed a terminal deletion in 22q13.32, not comprising the <jats:italic>NF2<\/jats:italic> gene. In tumour tissue, loss of the whole ring chromosome 22 including one <jats:italic>NF2<\/jats:italic> gene due to mitotic instability constituted the likely first hit, while a point mutation in the other allele of the <jats:italic>NF2<\/jats:italic> gene (c.784C&gt;T, p.R262X) was shown as second hit. We review all cases from the literature and suggest clinical guidelines for surveillance of patients with ring chromosome 22.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2010.01598.x","type":"journal-article","created":{"date-parts":[[2010,11,20]],"date-time":"2010-11-20T12:39:15Z","timestamp":1290256755000},"page":"82-87","source":"Crossref","is-referenced-by-count":27,"title":["Ring chromosome 22 and neurofibromatosis type II: proof of two\u2010hit model for the loss of the <i>NF2<\/i> gene in the development of meningioma"],"prefix":"10.1111","volume":"81","author":[{"given":"B","family":"Zirn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Arning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Bartels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Shoukier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Hoffjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,22]]},"reference":[{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33253"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.2.178"},{"key":"e_1_2_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-4608(87)90173-7"},{"key":"e_1_2_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470211"},{"key":"e_1_2_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1992.tb03233.x"},{"key":"e_1_2_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050467"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.016774"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-97"},{"key":"e_1_2_3_10_2","first-page":"603","article-title":"A clinical study of type 2 neurofibromatosis.","volume":"84","author":"Evans DG","year":"1992","journal-title":"Q J Med"},{"key":"e_1_2_3_11_2","first-page":"826.","article-title":"A novel moesin\u2010, ezrin\u2010, radixin\u2010like gene is a candidate for the neurofibromatosis 2 tumor suppressor.","volume":"75","author":"Trofatter JA","year":"1993","journal-title":"Cell"},{"key":"e_1_2_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_2_3_13_2","first-page":"304","article-title":"Comparative behavior of ring chromosomes.","volume":"22","author":"Kistenmacher ML","year":"1970","journal-title":"Am J Hum Genet"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31569"},{"key":"e_1_2_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.8.575"},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1933"},{"key":"e_1_2_3_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/522590"},{"key":"e_1_2_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906232107"},{"key":"e_1_2_3_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.20.5.380"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2010.01598.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2010.01598.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T16:14:48Z","timestamp":1698768888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2010.01598.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,22]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1111\/j.1399-0004.2010.01598.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2010.01598.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,22]]}}}