Title: Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis
Authors: Hellemans, Jan ×
Preobrazhenska, Olena
Willaert, Andy
Debeer, Philippe
Verdonk, Peter C M
Costa, Teresa
Janssens, K
Menten, Bjorn
Van Roy, Nadine
Vermeulen, Stefan J T
Savarirayan, Ravi
Van Hul, Wim
Vanhoenacker, Filip
Huylebroeck, Danny
De Paepe, Anne
Naeyaert, Jean-Marie
Vandesompele, Jo
Speleman, Frank
Verschueren, Kristin
Coucke, Paul J
Mortier, Geert R #
Issue Date: Oct-2004
Series Title: Nature genetics. vol:36 issue:11 pages:1213-1218
Abstract: Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells.
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Molecular Biology (Celgen) (-)
× corresponding author
# (joint) last author

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