{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:09:03Z","timestamp":1784714943907,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>L\u00e9ri\u2013Weill dyschondrosteosis (LWD) results from heterozygous mutations of the <jats:italic>SHOX<\/jats:italic> gene, with homozygosity or compound heterozygosity resulting in the more severe form, Langer mesomelic dysplasia (LMD). These mutations typically take the form of whole or partial gene deletions, point mutations within the coding sequence, or large (&gt;100\u2009kb) 3\u2032 deletions of downstream regulatory elements. We have analyzed the coding sequence of the <jats:italic>SHOX<\/jats:italic> gene and its downstream regulatory regions in a cohort of 377 individuals referred with symptoms of LWD, LMD or short stature. A causative mutation was identified in 68% of the probands with LWD or LMD (91\/134). In addition, a 47.5\u2009kb deletion was found 160\u2009kb downstream of the <jats:italic>SHOX<\/jats:italic> gene in 17 of the 377 patients (12% of the LWD referrals, 4.5% of all referrals). In 14 of these 17 patients, this was the only potentially causative abnormality detected (13 had symptoms consistent with LWD and one had short stature only), but the other three 47.5\u2009kb deletions were found in patients with an additional causative <jats:italic>SHOX<\/jats:italic> mutation (with symptoms of LWD rather than LMD). Parental samples were available on 14\/17 of these families, and analysis of these showed a more variable phenotype ranging from apparently unaffected to LWD. Breakpoint sequence analysis has shown that the 47.5\u2009kb deletion is identical in all 17 patients, most likely due to an ancient founder mutation rather than recurrence. This deletion was not seen in 471 normal controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001), providing further evidence for a phenotypic effect, albeit one with variable penetration. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.35919","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T05:12:04Z","timestamp":1367471524000},"page":"1329-1338","source":"Crossref","is-referenced-by-count":28,"title":["Diagnostic screening identifies a wide range of mutations involving the <i>SHOX<\/i> gene, including a common 47.5\u2009kb deletion 160\u2009kb downstream with a variable phenotypic effect"],"prefix":"10.1002","volume":"161","author":[{"given":"David J.","family":"Bunyan","sequence":"first","affiliation":[{"name":"Wessex Regional Genetics Laboratory Salisbury District Hospital, Salisbury Wiltshire SP2 8BJ UK"},{"name":"Faculty of Medicine University of Southampton Southampton, Hampshire SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Baker","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory Salisbury District Hospital, Salisbury Wiltshire SP2 8BJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory Salisbury District Hospital, Salisbury Wiltshire SP2 8BJ UK"},{"name":"Faculty of Medicine University of Southampton Southampton, Hampshire SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Simon","family":"Thomas","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory Salisbury District Hospital, Salisbury Wiltshire SP2 8BJ UK"},{"name":"Faculty of Medicine University of Southampton Southampton, Hampshire SO16 6YD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.64"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/449313"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/506390"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9456"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1689"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100678"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306685200"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31676"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.067785"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.216"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1341"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.51.197"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30852"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/499254"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn073"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000352"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.323"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.12.6289"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1148\/89.4.654"},{"key":"e_1_2_5_21_1","first-page":"216","article-title":"Phenotypic characterization of patients with deletions in the 3\u2032\u2010flanking SHOX region","volume":"76","author":"Losekoot M","year":"2011","journal-title":"Horm Res Paediatr"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307006200"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-169"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0218810401000424"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032230"},{"key":"e_1_2_5_26_1","first-page":"271","article-title":"Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: Results of an international study","volume":"58","author":"Neuhausen SL","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_27_1","first-page":"146","article-title":"Mutation spectrum of SHOX gene in 25 Italian pediatric patients with L\u00e9ri\u2013Weill dyschondrosteosis (LWD)","volume":"76","author":"Nicoletti A","year":"2011","journal-title":"Horm Res Paediatr"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-54"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.26.3083"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl470"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds019"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200402"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/431655"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnf056"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-70"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32914"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.35919","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.35919","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T14:43:35Z","timestamp":1698677015000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.35919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1002\/ajmg.a.35919"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.35919","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5]]}}}