{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:21:20Z","timestamp":1791897680663,"version":"4.3.4"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,10,14]]},"abstract":"<jats:p>\n                    Brachydactyly (BD) type A2 is an autosomal dominant hand malformation characterized by shortening and lateral deviation of the index fingers and, to a variable degree, shortening and deviation of the first and second toes. We performed linkage analysis in two unrelated German families and mapped a locus for BD type A2 to 4q21-q25. This interval includes the gene\n                    <jats:italic>bone morphogenetic protein receptor 1B<\/jats:italic>\n                    (\n                    <jats:italic>BMPR1B<\/jats:italic>\n                    ), a type I transmembrane serinethreonine kinase. In one family, we identified a T599 \u2192 A mutation changing an isoleucine into a lysine residue (I200K) within the glycine\/serine (GS) domain of BMPR1B, a region involved in phosphorylation of the receptor. In the other family we identified a C1456 \u2192 T mutation leading to an arginine-to-tryptophan amino acid change (R486W) in a highly conserved region C-terminal of the BMPR1B kinase domain. An\n                    <jats:italic>in vitro<\/jats:italic>\n                    kinase assay showed that the I200K mutation is kinase-deficient, whereas the R486W mutation has normal kinase activity, indicating a different pathogenic mechanism. Functional analyses with a micromass culture system revealed a strong inhibition of chondrogenesis by both mutant receptors. Overexpression of mutant\n                    <jats:italic>chBmpR1b in vivo<\/jats:italic>\n                    in chick embryos by using a retroviral system resulted either in a BD phenotype with shortening and\/or missing phalanges similar to the human phenotype or in severe hypoplasia of the entire limb. These findings imply that both mutations identified in human\n                    <jats:italic>BMPR1B<\/jats:italic>\n                    affect cartilage formation in a dominant-negative manner.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2133476100","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T15:05:46Z","timestamp":1066143946000},"page":"12277-12282","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":147,"title":["Mutations in\n                    <i>bone morphogenetic protein receptor 1B<\/i>\n                    cause brachydactyly type A2"],"prefix":"10.1073","volume":"100","author":[{"given":"Katarina","family":"Lehmann","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Seemann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigmar","family":"Stricker","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marai","family":"Sammar","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"S\u00fcring","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Majewski","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Tinschert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Grzeschik","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Knaus","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; Institut f\u00fcr Humangenetik, Universit\u00e4tsklinik D\u00fcsseldorf,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik, Humboldt-Universit\u00e4t, Charit\u00e9, Augustenburger Platz 1, 13353 Berlin, Germany; Max-Planck-Institut f\u00fcr Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; Institut f\u00fcr Physiologische Chemie II, Universit\u00e4t W\u00fcrzburg, Biozentrum, Am Hubland, 97074 W\u00fcrzburg, Germany; Genkartierungszentrum, Max-Delbr\u00fcck Zentrum f\u00fcr Molekulare Medizin, Robert-Roessle-Strasse 10, 13125 Berlin-Buch, Germany; 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