The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
Rudolf Happle - One of the best experts on this subject based on the ideXlab platform.
-
melorheostosis may originate as a type 2 segmental manifestation of Osteopoikilosis
American Journal of Medical Genetics Part A, 2004Co-Authors: Rudolf HappleAbstract:Melorheostosis is a non-hereditary disorder involving the bones in a segmental pattern, whereas Osteopoikilosis is a rather mild disseminated bone disorder inherited as an autosomal dominant trait. Interestingly, melorheostosis and Osteopoikilosis may sometimes occur together. In analogy to various autosomal dominant skin disorders for which a type 2 segmental manifestation has been postulated, melorheostosis may be best explained in such cases as a type 2 segmental Osteopoikilosis, resulting from early loss of the corresponding wild type allele at the gene locus of this autosomal dominant bone disorder. © 2003 Wiley-Liss, Inc.
-
Melorheostosis may originate as a type 2 segmental manifestation of Osteopoikilosis.
American journal of medical genetics. Part A, 2004Co-Authors: Rudolf HappleAbstract:Melorheostosis is a non-hereditary disorder involving the bones in a segmental pattern, whereas Osteopoikilosis is a rather mild disseminated bone disorder inherited as an autosomal dominant trait. Interestingly, melorheostosis and Osteopoikilosis may sometimes occur together. In analogy to various autosomal dominant skin disorders for which a type 2 segmental manifestation has been postulated, melorheostosis may be best explained in such cases as a type 2 segmental Osteopoikilosis, resulting from early loss of the corresponding wild type allele at the gene locus of this autosomal dominant bone disorder.
Robert P Davis - One of the best experts on this subject based on the ideXlab platform.
-
tc 99m mdp uptake in Osteopoikilosis
Clinical Nuclear Medicine, 1994Co-Authors: John A Mungovan, Glenn A Tung, Robert E Lambiase, Richard B Noto, Robert P DavisAbstract:: A Tc-99m bone scan of a patient with classic roentgenographic findings of Osteopoikilosis revealed multiple foci of increased activity that corresponded to many of the sclerotic foci on the roentgenograms. The authors presume that the abnormal bone scan in this patient reflects active osseous remodeling, similar to what has been observed in bone islands. Previous reports have emphasized the critical role of the radionuclide bone scan for distinguishing Osteopoikilosis from osteoblastic bone metastases in patients with a known or suspected primary malignancy. In a young patient, an abnormal bone scan does not exclude the diagnosis of Osteopoikilosis if the roentgenographic findings are characteristic of that entity.
Jan Hellemans - One of the best experts on this subject based on the ideXlab platform.
-
The Heterozygous Lemd3 ^ +/GT Mouse Is Not a Murine Model for Osteopoikilosis in Humans
Calcified Tissue International, 2009Co-Authors: Annelies Dheedene, Jan Hellemans, Steven Deleye, Steven Staelens, Stefaan Vandenberghe, Geert MortierAbstract:Osteopoikilosis and the Buschke-Ollendorff syndrome are skeletal dysplasias with hyperostotic lesions in the long bones. These disorders are caused by heterozygous loss-of-function mutations in the LEMD3 gene. LEMD3 codes for a protein of the inner nuclear membrane that, through interaction with R-SMADs, antagonizes the BMP and TGFβ1 pathway. It is suggested that the hyperostotic lesions in these disorders are caused by enhanced BMP and TGFβ1 signaling. The exact mechanism by which mutations in the LEMD3 gene lead to these bone lesions has not yet been unraveled precisely. To further assess this, an Lemd3 gene–trapped mouse was created in a gene-trapping program by Baygenomics. To investigate whether the heterozygous gene-trapped mouse is a good model for Osteopoikilosis in humans, we studied these mice radiologically with high-resolution micro-computed tomography (microCT) and histologically. X-ray images were evaluated by a trained radiologist, but no typical Osteopoikilosis lesions could be recognized. On all microCT reconstructed images a 3D cortical and trabecular quantitative analysis was performed, investigating different histomorphometric parameters ranging from percent bone volume, bone surface/volume ratio over trabecular thickness, separation, number, and pattern factor to structure model index and fractal dimension. No significant differences were found after a t -test statistical analysis. Also, histological analysis did not reveal lesions typical for Osteopoikilosis. We conclude that the heterozygous Lemd3 gene–trapped mouse is not a good model to study Osteopoikilosis and the Buschke-Ollendorff syndrome.
-
the heterozygous lemd3 gt mouse is not a murine model for Osteopoikilosis in humans
Calcified Tissue International, 2009Co-Authors: Annelies Dheedene, Jan Hellemans, Steven Deleye, Steven Staelens, Stefaan Vandenberghe, Geert MortierAbstract:Osteopoikilosis and the Buschke-Ollendorff syndrome are skeletal dysplasias with hyperostotic lesions in the long bones. These disorders are caused by heterozygous loss-of-function mutations in the LEMD3 gene. LEMD3 codes for a protein of the inner nuclear membrane that, through interaction with R-SMADs, antagonizes the BMP and TGFβ1 pathway. It is suggested that the hyperostotic lesions in these disorders are caused by enhanced BMP and TGFβ1 signaling. The exact mechanism by which mutations in the LEMD3 gene lead to these bone lesions has not yet been unraveled precisely. To further assess this, an Lemd3 gene–trapped mouse was created in a gene-trapping program by Baygenomics. To investigate whether the heterozygous gene-trapped mouse is a good model for Osteopoikilosis in humans, we studied these mice radiologically with high-resolution micro-computed tomography (microCT) and histologically. X-ray images were evaluated by a trained radiologist, but no typical Osteopoikilosis lesions could be recognized. On all microCT reconstructed images a 3D cortical and trabecular quantitative analysis was performed, investigating different histomorphometric parameters ranging from percent bone volume, bone surface/volume ratio over trabecular thickness, separation, number, and pattern factor to structure model index and fractal dimension. No significant differences were found after a t-test statistical analysis. Also, histological analysis did not reveal lesions typical for Osteopoikilosis. We conclude that the heterozygous Lemd3 gene–trapped mouse is not a good model to study Osteopoikilosis and the Buschke-Ollendorff syndrome.
-
Osteopoikilosis short stature and mental retardation as key features of a new microdeletion syndrome on 12q14
Journal of Medical Genetics, 2007Co-Authors: Bjorn Menten, Teresa Costa, Jan Hellemans, Karen Buysse, Farah R Zahir, Sara Jane Hamilton, Carrie Fagerstrom, George Anadiotis, Daniel J Kingsbury, Barbara McgillivrayAbstract:This report presents the detection of a heterozygous deletion at chromosome 12q14 in three unrelated patients with a similar phenotype consisting of mild mental retardation, failure to thrive in infancy, proportionate short stature and Osteopoikilosis as the most characteristic features. In each case, this interstitial deletion was found using molecular karyotyping. The deletion occurred as a de novo event and varied between 3.44 and 6 megabases (Mb) in size with a 3.44 Mb common deleted region. The deleted interval was not flanked by low‐copy repeats or segmental duplications. It contains 13 RefSeq genes, including LEMD3, which was previously shown to be the causal gene for Osteopoikilosis. The observation of Osteopoikilosis lesions should facilitate recognition of this new microdeletion syndrome among children with failure to thrive, short stature and learning disabilities.
-
germline lemd3 mutations are rare in sporadic patients with isolated melorheostosis
Human Mutation, 2006Co-Authors: Jan Hellemans, Philippe Debeer, Ravi Savarirayan, Lina Basel, Michael Wright, Klaus W. Kjaer, Andreas R Janecke, Peter Verdonk, Celia Moss, Johannes RothAbstract:To further explore the allelic heterogeneity within the group of LEMD3-related disorders, we have screened a larger series of patients including 5 probands with Osteopoikilosis or Buschke-Ollendorff syndrome (BOS), 2 families with the co-occurrence of melorheostosis and BOS, and 12 unrelated patients with isolated melorheostosis. Seven novel LEMD3 mutations were identified, all predicted to result in loss-of-function of the protein. We confirm that loss-of-function mutations in the LEMD3 gene can result in either Osteopoikilosis or BOS. However, LEMD3 germline mutations were only found in two melorheostosis patients belonging to a different BOS family and one sporadic patient with melorheostosis. The additional presence of Osteopoikilosis lesions in these patients seemed to distinguish them from the group of sporadic melorheostosis patients where no germline LEMD3 mutation was identified. Somatic mosaicism for a LEMD3 mutation in the latter group was also not observed, and therefore we must conclude that the genetic defect in the majority of sporadic and isolated melorheostosis remains unknown. © 2006 Wiley-Liss, Inc.
-
loss of function mutations in lemd3 result in Osteopoikilosis buschke ollendorff syndrome and melorheostosis
Nature Genetics, 2004Co-Authors: Jan Hellemans, Philippe Debeer, Olena Preobrazhenska, Teresa Costa, Katrien Janssens, Bjorn Menten, Andy Willaert, Peter Verdonk, Stefan Vermeulen, Ravi SavarirayanAbstract:Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density1. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic2,3,4. 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 embryogenesis5. In this study, LEMD3 interacted with BMP and activin-TGFβ receptor–activated Smads and antagonized both signaling pathways in human cells.
John A Mungovan - One of the best experts on this subject based on the ideXlab platform.
-
tc 99m mdp uptake in Osteopoikilosis
Clinical Nuclear Medicine, 1994Co-Authors: John A Mungovan, Glenn A Tung, Robert E Lambiase, Richard B Noto, Robert P DavisAbstract:: A Tc-99m bone scan of a patient with classic roentgenographic findings of Osteopoikilosis revealed multiple foci of increased activity that corresponded to many of the sclerotic foci on the roentgenograms. The authors presume that the abnormal bone scan in this patient reflects active osseous remodeling, similar to what has been observed in bone islands. Previous reports have emphasized the critical role of the radionuclide bone scan for distinguishing Osteopoikilosis from osteoblastic bone metastases in patients with a known or suspected primary malignancy. In a young patient, an abnormal bone scan does not exclude the diagnosis of Osteopoikilosis if the roentgenographic findings are characteristic of that entity.
Thomas Eggermann - One of the best experts on this subject based on the ideXlab platform.
-
submicroscopic chromosomal imbalances in idiopathic silver russell syndrome srs the srs phenotype overlaps with the 12q14 microdeletion syndrome
Journal of Medical Genetics, 2010Co-Authors: Sabrina Spengler, Nadine Schonherr, Gerhard Binder, Hartmut A Wollmann, Susanne Frickeotto, Reinhard Muhlenberg, Bernd Denecke, Michael Baudis, Thomas EggermannAbstract:Silver–Russell syndrome (SRS) is a heterogeneous disorder associated with intrauterine and postnatal growth restriction, body asymmetry, a relative macrocephaly, a characteristic triangular face and further dysmorphisms. In about 50% of patients, genetic/epigenetic alterations can be detected: >38% of patients show a hypomethylation of the IGF2/H19 imprinting region in 11p15, whereas the additional 10% carry a maternal uniparental disomy of chromosome 7. In single cases, cytogenetic aberrations can be detected. Nevertheless, there still remain 50% of SRS patients without known genetic/epigenetic alterations. To find out whether submicroscopic imbalances contribute to the aetiology of SRS, 20 idiopathic SRS patients were screened with the Affymetrix GeneChip Human Mapping 500 K array set. Apart from known apathogenic copy number variations, we identified one patient with a 12q14 microdeletion. The 12q14 microdeletion syndrome is characterised by dwarfism but it additionally includes mental retardation and Osteopoikilosis. The deletion in our patient is smaller than those in the 12q14 microdeletion carriers but it also affects the LEMD3 and the HMGA2 genes. LEMD3 haploinsufficiency and point mutations have been previously associated with Osteopoikilosis but radiographs of our patient at the age of 16 years did not reveal any hint for Osteopoikilosis lesions. Haploinsufficiency of HMGA2 is probably responsible for aberrant growth in 12q14 microdeletion syndrome. However, in this study, a general role of HMGA2 mutations for SRS was excluded by sequencing of 20 idiopathic patients. In conclusion, our results exclude a common cryptic chromosomal imbalance in idiopathic SRS patients but show that chromosomal aberrations are relevant in this disease. Thus, molecular karyotyping is indicated in SRS and should be included in the diagnostic algorithm.
