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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling
American Journal of Human Genetics, Volume 87, No. 6, Year 2010
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Description
Altered Bone Morphogenetic Protein (BMP) signaling leads to multiple developmental defects, including brachydactyly and deafness. Here we identify chondroitin synthase 1 (CHSY1) as a potential mediator of BMP effects. We show that loss of human CHSY1 function causes autosomal-recessive Temtamy preaxial brachydactyly syndrome (TPBS), mainly characterized by limb malformations, short stature, and hearing loss. After mapping the TPBS locus to chromosome 15q26-qterm, we identified causative mutations in five consanguineous TPBS families. In zebrafish, antisense-mediated chsy1 knockdown causes defects in multiple developmental processes, some of which are likely to also be causative in the etiology of TPBS. In the inner ears of zebrafish larvae, chsy1 is expressed similarly to the BMP inhibitor dan and in a complementary fashion to bmp2b. Furthermore, unrestricted Bmp2b signaling or loss of Dan activity leads to reduced chsy1 expression and, during epithelial morphogenesis, defects similar to those that occur upon Chsy1 inactivation, indicating that Bmp signaling affects inner-ear development by repressing chsy1. In addition, we obtained strikingly similar zebrafish phenotypes after chsy1 overexpression, which might explain why, in humans, brachydactyly can be caused by mutations leading either to loss or to gain of BMP signaling. © 2010 by The American Society of Human Genetics. All rights reserved..
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2997369/bin/mmc1.pdf
Authors & Co-Authors
Li, Yun
Germany, Koln
Universität zu Köln
Germany, Koln
Uniklinik Köln
Laue, Kathrin
Germany, Koln
Universität zu Köln
Temtamy, Samia Ali Li
Egypt, Giza
National Research Centre
Aglan, Mona Sabry
Egypt, Giza
National Research Centre
Kotan, L. Damla
Turkey, Adana
Çukurova Üniversitesi
Yigit, Gökhan
Germany, Koln
Universität zu Köln
Germany, Koln
Uniklinik Köln
Canan, Husniye
Turkey, Adana
Çukurova Üniversitesi
Pawlik, Barbara
Germany, Koln
Universität zu Köln
Germany, Koln
Uniklinik Köln
Nürnberg, Gudrun
Germany, Koln
Universität zu Köln
Germany, Koln
Medizinische Fakultät
Wakeling, Emma L.
Unknown Affiliation
Quarrell, Oliver W.J.
United Kingdom, Sheffield
Sheffield Children's Hospital
Baessmann, Ingelore
Germany, Koln
Medizinische Fakultät
Lanktree, Matthew B.
Canada, London
Robarts Research Institute
Yilmaz, Mustafa
Turkey, Adana
Çukurova Üniversitesi
Hegele, Robert A.
Canada, London
Robarts Research Institute
Amr, Khalda Sayed
Egypt, Giza
National Research Centre
May, Klaus W.
Germany, Munich
Genomatix ag
Nürnberg, Peter
Germany, Koln
Universität zu Köln
Germany, Koln
Medizinische Fakultät
Topaloǧlu, Ali Kemal
Turkey, Adana
Çukurova Üniversitesi
Hammerschmidt, Matthias
Germany, Koln
Universität zu Köln
Wollnik, Bernd
Germany, Koln
Universität zu Köln
Germany, Koln
Uniklinik Köln
Statistics
Citations: 82
Authors: 21
Affiliations: 8
Identifiers
Doi:
10.1016/j.ajhg.2010.10.003
ISSN:
00029297
Research Areas
Disability
Genetics And Genomics