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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2003-10-15
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pubmed:abstractText |
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 bone morphogenetic protein receptor 1B (BMPR1B), a type I transmembrane serinethreonine kinase. In one family, we identified a T599 --> 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 --> 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 in vitro 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 chBmpR1b in vivo 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 BMPR1B affect cartilage formation in a dominant-negative manner.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-10700182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-10712517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-10948551,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-10973254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-10986040,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11057902,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11251079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11259271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11320249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11381269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11416163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11455389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11553725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11583628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11784015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11934153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-11969258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-12040180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-1304821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-7390514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-7774578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-8145850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-8614838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-8702914,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-8722477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-9178898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-9288091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-9303535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14523231-9608511
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:GrzeschikKarl-HeinzKH,
pubmed-author:KnausPetraP,
pubmed-author:LehmannKatarinaK,
pubmed-author:MüllerDietmarD,
pubmed-author:MajewskiFrankF,
pubmed-author:MeyerBirgitB,
pubmed-author:MundlosStefanS,
pubmed-author:NürnbergPeterP,
pubmed-author:SüringKatrinK,
pubmed-author:SammarMaraiM,
pubmed-author:SeemannPetraP,
pubmed-author:StrickerSigmarS,
pubmed-author:TinschertSigridS
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12277-82
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14523231-Amino Acid Sequence,
pubmed-meshheading:14523231-Animals,
pubmed-meshheading:14523231-Base Sequence,
pubmed-meshheading:14523231-Bone Morphogenetic Protein Receptors, Type I,
pubmed-meshheading:14523231-Cartilage,
pubmed-meshheading:14523231-Chick Embryo,
pubmed-meshheading:14523231-Chondrogenesis,
pubmed-meshheading:14523231-Chromosome Mapping,
pubmed-meshheading:14523231-Chromosomes, Human, Pair 4,
pubmed-meshheading:14523231-DNA, Complementary,
pubmed-meshheading:14523231-Female,
pubmed-meshheading:14523231-Genes, Dominant,
pubmed-meshheading:14523231-Humans,
pubmed-meshheading:14523231-Limb Deformities, Congenital,
pubmed-meshheading:14523231-Male,
pubmed-meshheading:14523231-Molecular Sequence Data,
pubmed-meshheading:14523231-Mutation, Missense,
pubmed-meshheading:14523231-Pedigree,
pubmed-meshheading:14523231-Phenotype,
pubmed-meshheading:14523231-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14523231-Receptors, Growth Factor,
pubmed-meshheading:14523231-Sequence Homology, Amino Acid
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pubmed:year |
2003
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pubmed:articleTitle |
Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.
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pubmed:affiliation |
Institut für Medizinische Genetik, Humboldt-Universität, Charité, Augustenburger Platz 1, 13353 Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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