The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Philippe Debeer - One of the best experts on this subject based on the ideXlab platform.
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germline lemd3 mutations are rare in sporadic patients with isolated Melorheostosis
Human Mutation, 2006Co-Authors: Jan Hellemans, Philippe Debeer, Michael Wright, Andreas R Janecke, Klaus W Kjaer, Peter Verdonk, Ravi Savarirayan, Lina Basel, 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.
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loss of function mutations in lemd3 result in osteopoikilosis buschke ollendorff syndrome and Melorheostosis
Nature Genetics, 2004Co-Authors: Jan Hellemans, Philippe Debeer, Peter Verdonk, Olena Preobrazhenska, Andy Willaert, Teresa Costa, Katrien Janssens, Bjorn Menten, 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.
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Melorheostosis in a family with autosomal dominant osteopoikilosis report of a third family
American Journal of Medical Genetics Part A, 2003Co-Authors: Philippe Debeer, E Pykels, Johan Lammens, Koenraad Devriendt, J P FrynsAbstract:We describe a three-generation family with clinical and radiological findings of osteopoikilosis in five and Melorheostosis in one individual. The co-occurrence of both rare bone disorders suggests that both conditions might be related as suggested previously by Butkus et al. [1997: Am J Med Genet 72:43–46] and Nevin et al. [1999: Am J Med Genet 82:409–414]. The findings in this family strengthen the hypothesis that osteopoikilosis is an autosomal dominant condition and that an early postzygotic second hit mutation in the second allele results in Melorheostosis. © 2003 Wiley-Liss, Inc.
Bart L. Clarke - One of the best experts on this subject based on the ideXlab platform.
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Melorheostosis: a Rare Sclerosing Bone Dysplasia
Current Osteoporosis Reports, 2017Co-Authors: Anupam Kotwal, Bart L. ClarkeAbstract:Purpose of Review Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we describe the natural history, radiological features, proposed pathogenesis, and management options for this debilitating condition. Recent Findings Since its first description in 1922, about 400 cases of Melorheostosis have been reported, either as single reports or in small case series. Melorheostosis affects the appendicular skeleton more commonly than the axial skeleton and usually presents with lower limb deformity. Diagnosis is based on a combination of clinical and radiological features that help differentiate this condition from other sclerosing bone dysplasias. LEM domain-containing protein 3 (LEMD3) gene mutations have been demonstrated in several familial cases, but these have been more strongly correlated with other hereditary dysplasias, such as osteopoikilosis, and are not thought to be the causative gene for Melorheostosis. The exact etiology of classic sporadically occurring Melorheostosis remains unknown, with possible causes being somatic LEMD3 mutations, somatic mutations in the bone morphogenetic protein/transforming growth factor-beta pathway, mutations in multiple genes, or other non-genetic causes. Management in recent years has involved nitrogen-containing bisphosphonates in addition to traditional orthopedic surgical approaches and physical therapy. Summary Melorheostosis may present as mixed or atypical osseous involvement in addition to the classically described “dripping candle wax” appearance of hyperostosis. Some patients may have overlap with osteopoikilosis or Buschke–Ollendorff syndrome. In the future, better characterization of genetic and developmental factors predisposing to Melorheostosis may lead to the development of targeted therapy for this condition, as well as for more commonly encountered skeletal abnormalities.
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Melorheostosis a rare sclerosing bone dysplasia
Current Osteoporosis Reports, 2017Co-Authors: Anupam Kotwal, Bart L. ClarkeAbstract:Melorheostosis is a rare sclerosing bone dysplasia that affects both cortical bone and adjacent soft tissue structures in a sclerotomal distribution. In this review, we describe the natural history, radiological features, proposed pathogenesis, and management options for this debilitating condition. Since its first description in 1922, about 400 cases of Melorheostosis have been reported, either as single reports or in small case series. Melorheostosis affects the appendicular skeleton more commonly than the axial skeleton and usually presents with lower limb deformity. Diagnosis is based on a combination of clinical and radiological features that help differentiate this condition from other sclerosing bone dysplasias. LEM domain-containing protein 3 (LEMD3) gene mutations have been demonstrated in several familial cases, but these have been more strongly correlated with other hereditary dysplasias, such as osteopoikilosis, and are not thought to be the causative gene for Melorheostosis. The exact etiology of classic sporadically occurring Melorheostosis remains unknown, with possible causes being somatic LEMD3 mutations, somatic mutations in the bone morphogenetic protein/transforming growth factor-beta pathway, mutations in multiple genes, or other non-genetic causes. Management in recent years has involved nitrogen-containing bisphosphonates in addition to traditional orthopedic surgical approaches and physical therapy. Melorheostosis may present as mixed or atypical osseous involvement in addition to the classically described “dripping candle wax” appearance of hyperostosis. Some patients may have overlap with osteopoikilosis or Buschke–Ollendorff syndrome. In the future, better characterization of genetic and developmental factors predisposing to Melorheostosis may lead to the development of targeted therapy for this condition, as well as for more commonly encountered skeletal abnormalities.
Jan Hellemans - One of the best experts on this subject based on the ideXlab platform.
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germline lemd3 mutations are rare in sporadic patients with isolated Melorheostosis
Human Mutation, 2006Co-Authors: Jan Hellemans, Philippe Debeer, Michael Wright, Andreas R Janecke, Klaus W Kjaer, Peter Verdonk, Ravi Savarirayan, Lina Basel, 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.
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loss of function mutations in lemd3 result in osteopoikilosis buschke ollendorff syndrome and Melorheostosis
Nature Genetics, 2004Co-Authors: Jan Hellemans, Philippe Debeer, Peter Verdonk, Olena Preobrazhenska, Andy Willaert, Teresa Costa, Katrien Janssens, Bjorn Menten, 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.
N C Nevin - One of the best experts on this subject based on the ideXlab platform.
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Melorheostosis in a family with autosomal dominant osteopoikilosis
American Journal of Medical Genetics, 1999Co-Authors: N C Nevin, Paul S Thomas, Richard I Davis, Harry G CowieAbstract:We describe a 19-year-old woman with Melorheostosis and osteopoikilosis (mixed sclerosing bone dysplasia). Her sister and mother had osteopoikilosis, but no evidence of Melorheostosis. Isolated Melorheostosis and Melorheostosis with osteopoikilosis are sporadic disorders. Osteopoikilosis is an autosomal dominant trait. Mixed sclerosing bone dysplasia in a family with autosomal dominant osteopoikilosis raises the possibility that the two bone disorders may be related. This family and that of Butkus et al. [1997: Am J Med Genet 72:43–46] suggest that the Melorheostosis could be due to a second mutation at the same locus as that which causes autosomal dominant osteopoikilosis. Am. J. Med. Genet. 82:409–414, 1999. © 1999 Wiley-Liss, Inc.
Ravi Savarirayan - One of the best experts on this subject based on the ideXlab platform.
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germline lemd3 mutations are rare in sporadic patients with isolated Melorheostosis
Human Mutation, 2006Co-Authors: Jan Hellemans, Philippe Debeer, Michael Wright, Andreas R Janecke, Klaus W Kjaer, Peter Verdonk, Ravi Savarirayan, Lina Basel, 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.
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loss of function mutations in lemd3 result in osteopoikilosis buschke ollendorff syndrome and Melorheostosis
Nature Genetics, 2004Co-Authors: Jan Hellemans, Philippe Debeer, Peter Verdonk, Olena Preobrazhenska, Andy Willaert, Teresa Costa, Katrien Janssens, Bjorn Menten, 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.