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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 541871.0, MPI für molekulare Genetik / Research Group Development and Disease
Deletion and point mutations of PTHLH cause brachydactyly type E.
Authors:Klopocki, E.; Hennig, B. P.; Dathe, K.; Koll, R.; de Ravel, T.; Baten, E.; Blom, E.; Gillerot, Y.; Weigel, J. F.; Krüger, G.; Hiort, O.; Seemann, P.; Mundlos, S.
Language:English
Research Context:his work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG; KL 2158/2-1) to E.K., K.D., and S.M.
Date of Publication (YYYY-MM-DD):2010-03-12
Title of Journal:The American Journal of Human Genetics
Journal Abbrev.:Am J Hum Genet
Volume:86
Issue / Number:3
Start Page:434
End Page:439
Copyright:Copyright © 2010 The American Society of Human Genetics Published by Elsevier Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Autosomal-dominant brachydactyly type E (BDE) is a congenital limb malformation characterized by small hands and feet predominantly as a result of shortened metacarpals and metatarsals. In a large pedigree with BDE, short stature, and learning disabilities, we detected a microdeletion of approximately 900 kb encompassing PTHLH, the gene coding for parathyroid hormone related protein (PTHRP). PTHRP is known to regulate the balance between chondrocyte proliferation and the onset of hypertrophic differentiation during endochondral bone development. Inactivation of Pthrp in mice results in short-limbed dwarfism because of premature differentiation of chondrocyte. On the basis of our initial finding, we tested further individuals with BDE and short stature for mutations in PTHLH. We identified two missense (L44P and L60P), a nonstop (X178WextX( *)54), and a nonsense (K120X) mutation. The missense mutation L60P was tested in chicken micromass culture with the replication-competent avian sarcoma leukosis virus retroviral expression system and was shown to result in a loss of function. Thus, loss-of-function mutations in PTHLH cause BDE with short stature.
Comment of the Author/Creator:Corresponding author: Stefan Mundlos
Max-Planck-Institut für Molekulare Genetik, 14195 Berlin, Germany
stefan.mundlos@charite.de
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institut für Medizinische Genetik, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany;
2.Centre for Human Genetics, University Hospital Leuven, 3000 Leuven, Belgium;
3.AZ Saint Lucas, 8310 Brugge, Belgium;
4.Department of Clinical Genetics, Maastricht University Center, 6200 Maastricht, Netherlands
5.Centre de Génétique Humaine, Cliniques Universitaires St. Luc, 1200 Brussels, Belgium;
6.University Children's Hospital, 04103 Leipzig, Germany;
7.Abteilung Medizinische Genetik, Universitätsklinikum Rostock, 18057 Rostock, Germany;
8.Departments of Pediatrics, University of Lübeck, 23538 Lübeck, Germany;
9.Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 13353 Berlin, Germany.
Identifiers:ISSN:0002-9297 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/20170896 [ID No:2]
DOI:10.1016/j.ajhg.2010.01.023 [ID No:3]
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