{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:41:41Z","timestamp":1777952501755,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,9,24]],"date-time":"2002-09-24T00:00:00Z","timestamp":1032825600000},"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":[[2003,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>CDMP\u20101<\/jats:italic>, a cartilage\u2010specific member of the TGF\u00df superfamily of secreted signaling molecules, plays a key role in chondrogenesis, growth and patterning of the developing vertebrate skeleton. Homozygous <jats:italic>CDMP\u20101<\/jats:italic> mutations cause Hunter\u2010Thompson and Grebe types of acromesomelic chondrodysplasia and DuPan syndrome in humans, as well as <jats:italic>brachypodism<\/jats:italic> in mice, while heterozygous mutations cause brachydactyly type C (BDC). We present clinical and radiographic data from three unrelated families in which 12 members share the same heterozygous <jats:italic>CDMP\u20101<\/jats:italic> mutation, an insertion (insG206), resulting in a frameshift predicted to cause functional haploinsufficiency. Although eight mutation carriers display BDC, four have normal hands and feet, confirming nonpenetrance of BDC with <jats:italic>CDMP\u20101<\/jats:italic> mutations. In addition, several carriers have other skeletal abnormalities, including severe bilateral vertical talus (in two), developmental hip dysplasia (in one), and short stature (in two, who are otherwise unaffected). Premature vertebral end\u2010plate disease was observed in four mutation carriers and was associated with spondylolysis and spondylolisthesis in three of these. Axial skeletal involvement has not been previously reported in association with <jats:italic>CDMP\u20101<\/jats:italic> mutations. This finding is consistent with <jats:italic>CDMP\u20101<\/jats:italic> expression in human hypertrophic chondrocytes, which are present in the ring epiphyses of vertebral end plates. Phenotypic variation in BDC has previously been attributed either to locus heterogeneity or to the varied functional effects of different <jats:italic>CDMP\u20101<\/jats:italic> mutations. The remarkable range of phenotypes caused by this identical <jats:italic>CDMP\u20101<\/jats:italic> mutation in these families emphasizes the crucial role of genetic background, stochastic variation and\/or environmental factors in modifying the observed phenotype. Our findings illustrate that nonpenetrance for the typical features of BDC can be appreciable and that atypical skeletal features that have been reported in some patients with BDC (i.e., clubfoot, short stature, spondylolysis) may also result from <jats:italic>CDMP\u20101<\/jats:italic> mutation. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.10924","type":"journal-article","created":{"date-parts":[[2003,2,5]],"date-time":"2003-02-05T06:12:40Z","timestamp":1044425560000},"page":"136-142","source":"Crossref","is-referenced-by-count":46,"title":["Broad phenotypic spectrum caused by an identical heterozygous <i>CDMP\u20101<\/i> mutation in three unrelated families"],"prefix":"10.1002","volume":"117A","author":[{"given":"Ravi","family":"Savarirayan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan M.","family":"White","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances R.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"John M.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin B.","family":"Delatycki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph S.","family":"Lachman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Rimoin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Everman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew L.","family":"Warman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,9,24]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1","volume-title":"The treasury of human inheritance","author":"Bell J","year":"1951"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002517-199902000-00011"},{"key":"e_1_2_6_4_1","first-page":"28227","article-title":"Cartilage\u2010derived morphogenetic proteins","volume":"269","author":"Chang SC","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_6_5_1","first-page":"A1647","article-title":"Additional CDMP1 mutations suggest that brachydactyly type C is locus homogeneous and incompletely penetrant","volume":"65","author":"Everman DB","year":"1999","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.1.36"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320040208"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.6.1305"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20010122)98:3<256::AID-AJMG1088>3.0.CO;2-D"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1963.tb01976.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3171\/spi.2001.94.1.0068"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-18"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0590"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19970131)68:3<369::AID-AJMG23>3.0.CO;2-Q"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002470000181"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.105.4.860"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/368639a0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-315"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-58"},{"key":"e_1_2_6_20_1","first-page":"A2638","article-title":"Mutations in the cartilage\u2010derived morphogenetic protein\u20101, in kindred affected with Grebe type severe short limb dwarfism and DuPan syndrome","volume":"69","author":"Ul Haque MF","year":"2001","journal-title":"Am J Hum Genet"}],"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.10924","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.10924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T16:59:59Z","timestamp":1700153999000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.10924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,9,24]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,3]]}},"alternative-id":["10.1002\/ajmg.a.10924"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.10924","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,9,24]]}}}