{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:47:01Z","timestamp":1793065621401,"version":"4.5.0"},"reference-count":15,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p>Hypochondroplasia (HCH) is an autosomal dominant condition characterised by short stature, micromelia, and lumbar lordosis. In a series of 29 HCH probands (13 sporadic cases, 16 familial cases), we tested their DNA for the N540K recurrent mutation previously described in the proximal tyrosine kinase domain of the FGFR3 gene on chromosome 4p16.3, and we detected this mutation in 21\/29 HCH patients. Interestingly, three familial cases were clearly unlinked to chromosome 4p16.3. Reviewing the clinical and radiological manifestations of the disease a posteriori, we observed that the N540K mutation was associated with relative macrocrania with a high and large forehead and short hands. By contrast, in the three pedigrees inconsistent with linkage to chromosome 4p16.3, the clinical phenotype was milder, macrocephaly and shortening of the long bones was less obvious, the hands were normal, and no metaphyseal flaring was noted. This study supports the view that HCH is a clinically and genetically heterogeneous condition.<\/jats:p>","DOI":"10.1136\/jmg.33.9.749","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"749-752","source":"Crossref","is-referenced-by-count":108,"title":["Clinical and genetic heterogeneity of hypochondroplasia."],"prefix":"10.1136","volume":"33","author":[{"given":"F","family":"Rousseau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bonaventure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Legeai-Mallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Weissenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Maroteaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Le Merrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"key":"ref_1","first-page":"157","article-title":"Achondroplasie et chondrohypoplasie, contribution clinique. Nouv Iconog Salpet","volume":"26","author":"Ravenna, F.","year":"1913","unstructured":"Ravenna F. Achondroplasie et chondrohypoplasie, contribution clinique. Nouv Iconog Salpet 1913;26:157-84."},{"key":"ref_2","first-page":"105","article-title":"Hypochondroplasie: revue de 80 cas","volume":"45","author":"Maroteaux, P.; Falzon, P.","year":"1988","unstructured":"Maroteaux P, Falzon P. Hypochondroplasie: revue de 80 cas. Arch Fr Pediatr 1988;45:105-9.","journal-title":"Arch Fr Pediatr"},{"key":"ref_3","first-page":"508","article-title":"Achondroplasia and hypochondroplasia: clinical variation and spinal stenosis","volume":"63","author":"R, Wynne Davies; WK, Walsh; J, Gormley","year":"1981","unstructured":"Wynne Davies R, Walsh WK, Gormley J. Achondroplasia and hypochondroplasia: clinical variation and spinal stenosis. 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A gene for achondroplasia-hypochondroplasia maps to chromosome 4p. Nature Genet 1994;6:318-21.","journal-title":"Nature Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/371252a0","article-title":"Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia","volume":"371","author":"Rousseau, F.; Bonaventure, J.; Legeai-Mallet, L.","year":"1994","unstructured":"Rousseau F, Bonaventure J, Legeai-Mallet L, et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 1994;371:252-4.","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0092-8674(94)90302-6","article-title":"Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia","volume":"78","author":"Shiang, R.; Thompson, L.M.; Zhu, Y.Z.","year":"1994","unstructured":"Shiang R, Thompson LM, Zhu YZ, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994;78:335-42.","journal-title":"Cell"},{"key":"ref_10","first-page":"368","article-title":"Achondroplasia is defined by recurrent G380R mutations of FGFR3","volume":"56","author":"Bellus, G.A.; Hefferon, T.W.; Ortiz de Luna, R.I.","year":"1995","unstructured":"Bellus GA, Hefferon TW, Ortiz de Luna RI, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Anm Hum Genet 1995;56:368-73.","journal-title":"Anm Hum Genet"},{"key":"ref_11","first-page":"505","article-title":"Blanton SH. Confirmatory linkage of hypochondroplasia to chromosome arm 4p","volume-title":"Am; Med Genet","volume":"57","author":"Hecht, J.T.; Herrera, C.A.; Greenhaw, G.A.; Francomano, C.A.; Bellus, G.A.","year":"1995","unstructured":"Hecht JT, Herrera CA, Greenhaw GA, Francomano CA, Bellus GA, Blanton SH. Confirmatory linkage of hypochondroplasia to chromosome arm 4p. Am; Med Genet 1995;57:505-6."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng0795-357","article-title":"A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia","volume":"10","author":"Bellus, G.A.; McIntosh, I.; Smith, E.A.","year":"1995","unstructured":"Bellus GA, McIntosh I, Smith EA, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nature Genet 1995;10:357-9.","journal-title":"Nature Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1093\/hmg\/4.11.2097","article-title":"A common FGFR3 gene mutation in hypochondroplasia","volume":"4","author":"Prinos, P.; Costa, T.; Sommer, A.; Tsipouras, Kilpatrick M.W.; P.","year":"1995","unstructured":"Prinos P, Costa T, Sommer A, Kilpatrick MW Tsipouras P. A common FGFR3 gene mutation in hypochondroplasia. 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Possible genetic heterogeneity in hypochondroplasia. _7 Med Genet 1995;32:492-3."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.9.749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:59:26Z","timestamp":1760734766000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.9.749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,9]]},"references-count":15,"journal-issue":{"issue":"9","published-online":{"date-parts":[[1996,9,1]]},"published-print":{"date-parts":[[1996,9]]}},"alternative-id":["10.1136\/jmg.33.9.749"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.9.749","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,9]]}}}