{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:15:35Z","timestamp":1791288935627,"version":"4.3.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T00:00:00Z","timestamp":1215561600000},"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":[[2008,12]]},"abstract":"<jats:p>Nievergelt syndrome (NS) is an autosomal dominant mesomelic dysplasia characterized by specific deformities of the radius, ulna, fibula and a rhomboid shape of the tibia. Phenotypically overlapping conditions such as mesomelic dysplasia, Savarirayan\u2010type (MIM 605274), have been described, but their pathogenesis also remains unknown. We report on a girl with fibular agenesis, severely abnormal, triangular tibiae, urogenital tract malformations, failure to thrive, convulsions and recurrent apnoeas leading to respiratory arrest at the age of 4\u2003months. Her skeletal findings correspond to those of the mesomelic dysplasia, Savarirayan\u2010type recently described in two patients. In addition to the skeletal findings, our patient had central nervous system manifestations and developmental anomalies of the urogenital tract. In the patient described in this study, array comparative genomic hybridization (CGH) analysis revealed a <jats:italic>de novo <\/jats:italic>interstitial microdeletion of 500\u2003kb on chromosome 2q11.1 containing the <jats:italic>LAF4\/AFF3 <\/jats:italic>(lymphoid\u2010nuclear\u2010protein\u2010related AF4) gene. <jats:italic>In situ <\/jats:italic>hybridization analysis of <jats:italic>Laf4 <\/jats:italic>in mouse embryos revealed expression in the developing brain, in the limb buds and in the zeugopod corresponding to the limb phenotype. Haploinsufficiency for <jats:italic>LAF4\/AFF3 <\/jats:italic>is associated with limb, brain and urogenital malformations and specific changes of the tibia that are part of the NS spectrum.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2008.01050.x","type":"journal-article","created":{"date-parts":[[2009,1,23]],"date-time":"2009-01-23T10:23:27Z","timestamp":1232706207000},"page":"560-565","source":"Crossref","is-referenced-by-count":32,"title":["Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing <i>LAF4<\/i>"],"prefix":"10.1111","volume":"74","author":[{"given":"E","family":"Steichen\u2010Gersdorf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Ga\u00dfner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Superti\u2010Furga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Ullmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Stricker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Klopocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Mundlos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,11,20]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31483"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/377110"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20000904)94:1<59::AID-AJMG12>3.0.CO;2-2"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh700"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg0515s21"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10155"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31163"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.modgep.2006.05.014"},{"key":"e_1_2_8_10_2","first-page":"157","article-title":"Positiver Vaterschaftsnachweis auf Grund erblicher Missbildungen der Extremit\u00e4ten","volume":"19","author":"Nievergelt K","year":"1944","journal-title":"Arch Julius Klaus-Stiftung"},{"issue":"31","key":"e_1_2_8_11_2","first-page":"1202","article-title":"Familial mesomelial dwarfism (Nievergelt syndrome)","volume":"108","author":"Hess OM","year":"1978","journal-title":"Schweiz Med Wochenschr"},{"key":"e_1_2_8_12_2","first-page":"1126","volume-title":"Birth defects encyclopedia","author":"Kaitila I","year":"1990"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970502)70:1<48::AID-AJMG10>3.0.CO;2-X"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320370104"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10283"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31888"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10091"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10187"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206389"},{"issue":"5","key":"e_1_2_8_20_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1242\/dev.128.5.791","article-title":"Lilliputian: an AF4\/FMR2\u2010related protein that controls cell identity and cell growth","volume":"128","author":"Wittwer F","year":"2001","journal-title":"Development"},{"issue":"2","key":"e_1_2_8_21_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/genetics\/157.2.717","article-title":"A screen for modifiers of decapentaplegic mutant phenotypes identifies lilliputian, the only member of the Fragile\u2010X\/Burkitt\u2019s Lymphoma family of transcription factors in Drosophila melanogaster","volume":"157","author":"Su MA","year":"2001","journal-title":"Genetics"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6796"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2008.01050.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2008.01050.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T08:58:50Z","timestamp":1696928330000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2008.01050.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11,20]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1111\/j.1399-0004.2008.01050.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2008.01050.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":[[2008,11,20]]}}}