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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Faulty initiation of proteoglycan synthesis causes cardiac and joint defects
American Journal of Human Genetics, Volume 89, No. 1, Year 2011
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Description
Proteoglycans are a major component of extracellular matrix and contribute to normal embryonic and postnatal development by ensuring tissue stability and signaling functions.We studied five patients with recessive joint dislocations and congenital heart defects, including bicuspid aortic valve (BAV) and aortic root dilatation. We identified linkage to chromosome 11 and detected a mutation (c.830G>A, p.Arg277Gln) in B3GAT3, the gene coding for glucuronosyltransferase-I (GlcAT-I). The enzyme catalyzes an initial step in the synthesis of glycosaminoglycan side chains of proteoglycans. Patients' cells as well as recombinant mutant protein showed reduced glucuronyltransferase activity. Patient fibroblasts demonstrated decreased levels of dermatan sulfate, chondroitin sulfate, and heparan sulfate proteoglycans, indicating that the defect in linker synthesis affected all three lines of O-glycanated proteoglycans. Further studies demonstrated that GlcAT-I resides in the cis and cis-medial Golgi apparatus and is expressed in the affected tissues, i.e., heart, aorta, and bone. The study shows that reduced GlcAT-I activity impairs skeletal as well as heart development and results in variable combinations of heart malformations, including mitral valve prolapse, ventricular septal defect, and bicuspid aortic valve. The described family constitutes a syndrome characterized by heart defects and joint dislocations resulting from altered initiation of proteoglycan synthesis (Larsenlike syndrome, B3GAT3 type). © 2011 by The American Society of Human Genetics. All rights reserved.
Authors & Co-Authors
Baasanjav, Sevjidmaa
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Leipzig
Universitätsklinikum Leipzig Und Medizinische Fakultät
Al-Gazali, Lihadh I.
United Arab Emirates, Al Ain
College of Medicine and Health Sciences United Arab Emirates University
Hashiguchi, Taishi
Japan, Sapporo
Hokkaido University
Mizumoto, Shuji
Japan, Sapporo
Hokkaido University
Fischer, Björn
Germany, Berlin
Charité – Universitätsmedizin Berlin
Horn, Denise
Germany, Berlin
Charité – Universitätsmedizin Berlin
Seelow, Dominik
Germany, Berlin
Charité – Universitätsmedizin Berlin
Ali, Bassam R.
United Arab Emirates, Al Ain
College of Medicine and Health Sciences United Arab Emirates University
Aziz, Samir A.A.
Saudi Arabia
Ras al Khaimah
Langer, Ruth
United Arab Emirates, Al Ain
College of Medicine and Health Sciences United Arab Emirates University
Saleh, Ahmed A.H.
Saudi Arabia
Ras al Khaimah
Becker, Christian F.W.
Germany, Koln
Medizinische Fakultät
Nürnberg, Gudrun
Germany, Koln
Medizinische Fakultät
Cantagrel, Vincent
United States, La Jolla
Department of Neurosciences
Gleeson, Joseph G.
United States, La Jolla
Department of Neurosciences
Gomez, Delphine
France, Paris
Inserm
Michel, Jean Baptiste L.
France, Paris
Inserm
Stricker, Sigmar
Germany, Berlin
Max Planck Institute for Molecular Genetics
Lindner, Tom H.
Germany, Leipzig
Universitätsklinikum Leipzig Und Medizinische Fakultät
Nürnberg, Peter
Germany, Koln
Medizinische Fakultät
Sugahara, Kazuyuki
Japan, Sapporo
Hokkaido University
Mundlos, Stefan
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Hoffmann, Katrin Katrin
Germany, Berlin
Charité – Universitätsmedizin Berlin
Germany, Berlin
Max Planck Institute for Molecular Genetics
Germany, Halle
Martin-luther-universität Halle-wittenberg
Statistics
Citations: 111
Authors: 23
Affiliations: 10
Identifiers
Doi:
10.1016/j.ajhg.2011.05.021
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases