From the Cover: Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.

Lehmann K; Seemann P; Stricker SSammar MMeyer BSuring KMajewski FTinschert SGrzeschik KHMuller DKnaus PNurnberg PMundlos S

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >From the Cover: Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.

【24h】

From the Cover: Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.

机译：

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

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.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2003年第21期|12277-12282|共6页
作者
Lehmann K; Seemann P; Stricker SSammar MMeyer BSuring KMajewski FTinschert SGrzeschik KHMuller DKnaus PNurnberg PMundlos S;
展开▼
作者单位

Institut fur Medizinische Genetik, Humboldt-Universitat, Charite, Augustenburger Platz 1, 13353 Berlin, Germany.;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Mutation; receptor; Phosphotransferases; A2; 1B; 突变; 磷酸转移酶类;

相似文献

外文文献
中文文献

1. Bone Morphogenic Protein Type 2 Receptor Mutation-Independent Mechanisms of Disrupted Bone Morphogenetic Protein Signaling in Idiopathic Pulmonary Arterial Hypertension [J] . Barnes Jarrod W., Kucera Elif T., Tian LipingMellor Noel E.Dvorina NinaBaldwin William W. IIIAldred Micheala A.Farver Carol F.Comhair Suzy A. A.Aytekin MetinDweik Raed A. American journal of respiratory cell and molecular biology . 2016,第4期

机译：Bone Morphogenic Protein Type 2 Receptor Mutation-Independent Mechanisms of Disrupted Bone Morphogenetic Protein Signaling in Idiopathic Pulmonary Arterial Hypertension
2. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. [J] . Seemann P, Schwappacher R, Kjaer KWKrakow DLehmann KDawson KStricker SPohl JPloger FStaub ENickel JSebald WKnaus PMundlos S The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation . 2005,第9期

机译：Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2.
3. A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength [J] . Baudhuin M., Solban N., Cornwall-Brady M.Sako D.Kawamoto Y.Liharska K.Lath D.Bouxsein M.L.Underwood K.W.Ucran J.Kumar R.Pobre E.Grinberg A.Seehra J.Canalis E.Pearsall R.S.Croucher P.I. Proceedings of the National Academy of Sciences of the United States of America . 2012,第30期

机译：A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength
4. A novel type of familial hypercholesterolemia: Double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene [O] . Tada, Hayato, Kawashiri, Masa-aki, Ohtani, Rumiko, 2011

机译：a novel type of familial hypercholesterolemia: Double heterozygous mutations in LDL receptor and LDL receptor adaptor protein 1 gene

From the Cover: Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2.

摘要

著录项

相似文献

相关主题

期刊订阅