The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Jules G Leroy - One of the best experts on this subject based on the ideXlab platform.
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acanthosis nigricans in a child with mild Osteochondrodysplasia and k650q mutation in the fgfr3 gene
American Journal of Medical Genetics Part A, 2007Co-Authors: Jules G Leroy, Lieve Nuytinck, Jo Lambert, Jeanmarie Naeyaert, Geert MortierAbstract:A girl with a mild sporadic Osteochondrodysplasia (OCD) similar to hypochondroplasia but with significant short stature is reported. She has been followed clinically between the ages of 9 months and 14 years. Growth remained normal throughout childhood with stature evolving about 3.5 SDs under the mean for age. By 8 years of age gradually appearing acanthosis nigricans (AN) in the neck and flanks was histopathologically confirmed. It provided the new incentive to search for specific FGFR3 mutations associated with this dermatologic abnormality. This resulted in the identification of the 1948A>C transversion predicting the K650Q missense substitution in the FGFR3 protein. Besides the expansion of the phenotypic spectrum of FGFR3-related OCDs to HCH with AN, this observation underscores the continuing adverse effect of this specific mutation upon the normal inhibitory signaling of the receptor at least in epidermal cells.
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Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum.
American journal of human genetics, 1998Co-Authors: Michael D. Briggs, Jules G Leroy, Lieve Nuytinck, Geert Mortier, William G. Cole, Lily King, Steven S. Golik, Jacky Bonaventure, Anne De Paepe, Leslie G. BieseckerAbstract:Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant Osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm. nih.gov:80/htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP.
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blomstrand lethal Osteochondrodysplasia
American Journal of Medical Genetics, 1996Co-Authors: Jules G Leroy, Guy Keersmaeckers, M Coppens, Jan E Dumon, H RoelsAbstract:We present the clinical, roentgenographic, and histologic abnormalities in a stillborn infant with Blomstrand Osteochondrodysplasia. Parental consanguinity and multiplex occurrence in the patients' sibship confirm the hypothesis of autosomal recessive inheritance of this monogenic lethal entity. The unknown genetic defect interferes severely with skeletal growth through lack of chondrocyte multiplication and apparent uncoupling of the processes of enchondral ossification and skeletal growth.
Stephen P Robertson - One of the best experts on this subject based on the ideXlab platform.
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a new Osteochondrodysplasia with severe osteopenia preaxial polydactyly clefting and dysmorphic features resembling filamin related disorders
Prenatal Diagnosis, 2006Co-Authors: Marina Colombani, Nicole Laurent, Martine Le Merrer, Annelise Delezoide, Christel Thauvinrobinet, Frederic Huet, P Sagot, Stephanie Couvreur, Thierry Rousseau, Stephen P RobertsonAbstract:Background We report a 19-week gestation female foetus with a new syndrome characterised by increased nuchal translucency and severe micromelia with campomelia evident from the early second trimester. Methods and Results Cytogenetic studies performed on amniocytes revealed a normal female karyotype. Autopsy after termination of pregnancy showed facial dysmorphism, cleft palate, bowed, shortened limbs, hypoplasia of the preaxial elements in all four limbs with accompanying accessory ossification centres in the feet, and severe calvarial underossification. A diagnosis of otopalatodigital syndrome type 2, associated with mutations in FLNA, a gene encoding the cytoskeletal protein filamin A, was considered but discarded due to the severity of micromelia, early lethality, and the presence of generalised osteopenia instead of hyperostosis. The degree of undermodelling and campomelia was reminiscent of another group of conditions that include atelosteogenesis types 1 and 3, caused by mutations in FLNB. Sequencing analysis did not reveal any pathogenic mutation in the three paralogous filamin genes: FLNA, FLNB and FLNC. Conclusion Clinical, radiological and cytogenetic findings suggest that this phenotype is a new entity whose aetiopathogenesis may be functionally related to the filaminopathies. Copyright © 2006 John Wiley & Sons, Ltd.
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congenital hypertrichosis Osteochondrodysplasia and cardiomegaly cantu syndrome
American Journal of Medical Genetics, 1999Co-Authors: Stephen P Robertson, Edwin P Kirk, Francois P Bernier, Jeff Brereton, Anne M Turner, Agnes BankierAbstract:Cantu syndrome (hypertrichosis, Osteochondrodysplasia, cardiomegaly) is a rare condition, previously reported in 13 patients. We report on two additional patients with this disorder. One of the patients had pulmonary hypertension of unknown cause which was responsive to steroid therapy. She also had unusual, deep plantar creases, not reported previously in Cantu syndrome. Autosomal recessive inheritance has been suggested previously on the basis of sib recurrence in one family and consanguinity in another. We have performed a segregation analysis based on all reported families to date; the data indicate autosomal recessive inheritance is unlikely. A new dominant mutation or microdeletion syndrome are more likely possibilities, sib recurrence possibly representing gonadal mosaicism.
Katsushi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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insertional mutation in the golgb1 gene is associated with Osteochondrodysplasia and systemic edema in the ocd rat
Bone, 2011Co-Authors: Kentaro Katayama, Katsushi Suzuki, Tetsu Sasaki, Syo Goto, Kei Ogasawara, Hiromi Maru, Hiroetsu SuzukiAbstract:article i nfo Homozygous rats (ocd/ocd) of a mutant inbred strain, OCD (Osteochondrodysplasia), show osteochondrodys- plasia, systemic edema, cleft palate, protruding tongue, disproportionate dwarfism, and lethality immediately after birth. Their epiphyses show decreased levels of glycosaminoglycans and weak staining for extracellular matrix proteins. The epiphyseal chondrocytes have large vesicles and expanded endoplasmic reticulum and Golgi apparatus. These phenotypic features are inherited in an autosomal recessive manner, and the ocd locus responsible for these phenotypes has been mapped close to D11Mgh3 on rat chromosome 11. In the present study, we characterized the embryonic pathogenesis of ocd/ocd rats and identified the mutant gene. Subcutaneous edema in the dorsal portion was found at embryonic day (E) 16.5, and the other anomalies described above were apparent after E18.5 in ocd/ocd. Whole mount immunohistochemistry for Sox9 revealed that mesenchymal condensation was delayed in limb bud in ocd/ocd, and skeletal preparation showed that the progression of whole-body chondrogenesis was delayed in ocd/ocd. Histological and immunohistological analyses of the femur showed that cell proliferations of resting and proliferative zones of growth plate were significantly reduced in ocd/ocd embryos. Fine linkage mapping localized the ocd locus within 84 kb of positions 65,584-65,668 kb containing a part of Golgb1 gene on chromosome 11. Expression of Golgb1 mRNA was found in limb buds, somite derivatives and calvaria. Sequence analysis identified a 10-bp insertion in exon 13 of the Golgb1 gene in ocd/ocd rats. The Golgb1 gene encodes the COPI vesicle tethering factor, giantin. This insertion mutation causes a frame shift, and introduces a premature termination codon at codon 1082, leading to truncation of the C-terminal two thirds of giantin. By in-gel Western analysis using anti-giantin antibody that recognizes an epitope within 200 aa of the C-terminus, the expression of giantin was not detected in ocd/ocd embryos. As the C-terminal region of giantin is required for localization to the Golgi apparatus, these results strongly suggested that giantin is functionally defective in ocd/ocd rats. Therefore, we concluded that mutation of the Golgb1 gene is responsible for the phenotypic characteristics including Osteochondrodysplasia of ocd/ocd, and that giantin plays a pivotal role in multiple aspects of chondrogenesis.
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histochemical and immunohistochemical distribution of glycosaminoglycans type ii collagen and fibronectin in developing fetal cartilage of congenital Osteochondrodysplasia rat ocd ocd
Teratology, 1992Co-Authors: Keiichiro Kikukawa, Katsushi SuzukiAbstract:The Osteochondrodysplasia rat (ocd/ocd) is a lethal dwarfism. The ocd/ocd shows histological abnormalities of the epiphysis, characterized by a decrease in amount of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). The present study describes histochemical and immunohistochemical distributions of GAGs, type II collagen, and fibronectin (FN) in abnormal humeral cartilage of the ocd/ocd fetuses on days 16–21 of gestation. A wide-spread region with severe necrosis was observed in the cartilage on days 20 and 21. The affected cartilage has small amounts of ECM, irregular columnizations, thinner hypertrophic zones, and expanded and pyknotic chondrocytes on days 16–21 of gestation. The severely expanded chondrocytes did not have cytoplasmic glycogens on days 19–21. Reactions for chondroitin sulfate (CS) and hyaluronic acid (HA) in the ECM were consistently lower in ocd/ocd than in +/+ during the entire period of observation, although there were granules immunoreactive to CS within the chondrocytes of ocd/ocd. The distribution of type II collagen seemed normal in relatively normal regions in the affected cartilage. Strong reactions for CS, HA, type II collagen, and FN were present in the necrotic region on days 20 and 21 of gestation. These findings suggest that the affected chondrocyte may have some defects in releasing ECM substances, which may be released by the process of cell rupture. We hypothesize that some defects in releasing processes inherent to the ocd/ocd cartilage may relate to cellular differentiation and cell death. © 1992 Wiley-Liss, Inc.
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a histological and histochemical study on glycosaminoglycans in epiphysial cartilage of Osteochondrodysplasia rat ocd ocd
Connective Tissue Research, 1991Co-Authors: Keiichiro Kikukawa, Takayuki Kamei, Katsushi SuzukiAbstract:The Osteochondrodysplasia rat, inherited by a single autosomal recessive lethal gene ocd, shows a typical dwarfing syndrome with systemic subcutaneous edema. The skeletal system is most severely affected. The affected neonates are associated with cleft palate, abnormal kidney position and central nerve system malfunction. The present study describes histological and histochemical appearances of the affected epiphysial cartilage. Irregular columnization, thinner hypertrophic zone, swelled chondrocytes, tightly packed chondrocytes with a poor amount of cartilage matrix was found in the affected. The defining characteristic was a wide-spread degenerating area from the resting to hypertrophic zone. The extracellular matrix (ECM) reacted weakly for the glycosaminoglycans (GAGs). A reduced content of sialic acid in the ECM was suggested. It is concluded that the cartilage abnormalities in the ocd/ocd is a new type disease of Osteochondrodysplasia possibly due to some defects in GAGs and/or sialic acid metabolism.
Matthew L Warman - One of the best experts on this subject based on the ideXlab platform.
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acromesomelic dysplasia maroteaux type maps to human chromosome 9
American Journal of Human Genetics, 1998Co-Authors: Sarina G Kant, Alexander Polinkovsky, Stefan Mundlos, Bernhard Zabel, Ralph T W M Thomeer, Harmien M Zonderland, Lingyu Shih, Arie Van Haeringen, Matthew L WarmanAbstract:Acromesomelic dysplasias are skeletal disorders that disproportionately affect the middle and distal segments of the appendicular skeleton. We report genetic mapping studies in four families with acromesomelic dysplasia Maroteaux type (AMDM), an autosomal recessive Osteochondrodysplasia. A peak LOD score of 5.1 at recombination fraction 0 was obtained with fully informative markers on human chromosome 9. In three of the four families, the affected offspring are products of consanguineous marriages; if it is assumed that these affected offspring are homozygous by descent for the region containing the AMDM locus, a 6.9-cM AMDM candidate interval can be defined by markers D9S1853 and D9S1874. The mapping of the AMDM locus to human chromosome 9 indicates that AMDM is genetically distinct from the two other mapped acromesomelic dysplasias, Hunter-Thompson type and Grebe type, which are caused by mutations in CDMP1 on human chromosome 20.
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a mutation in the gene encoding the α2 chain of the fibril associated collagen ix col9a2 causes multiple epiphyseal dysplasia edm2
Nature Genetics, 1996Co-Authors: Y Muragaki, Björn Olsen, Matthew L Warman, Edwin C. M. Mariman, S E C Van Beersum, Merja Perala, J B A Van Mourik, B.c.j. HamelAbstract:Multiple epiphyseal dysplasia, an autosomal dominant disease, is among the more common inherited Osteochondrodysplasias. Symptoms range from stiffness and pain in large joints to frank osteoarthritis associated with short stature and stubby fingers1–7. Linkage analyses of multiple epiphyseal dysplasia families suggest at least three loci. One locus, EDM1, maps to chromosome 19 (ref. 4), and is caused by mutations in cartilage oligomeric matrix protein (COMP)8. Mutations in COMP have also been identified in patients with pseudoachon-droplasia (PSACH)8,9, consistent with previous analyses which suggested that EDM1 and PSACH could be allelic disorders10. A second locus, EDM2, maps to chromosome 1 in the vicinity of the COL9A2 gene6. Finally, exclusion of EDM1 and EDM2 in other families suggests the existence of at least one additional locus11. We now show that affected members of a large kindred with multiple epiphyseal dysplasia linked to the EDM2 locus are heterozygous for a splice site mutation within COL9A2, causing exon skipping during RNA splicing and an in-frame loss of 12 amino acid residues within the α2(IX) collagen chain. The results provide the first in vivo evidence for the role of collagen IX in human articular cartilage.
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a type x collagen mutation causes schmid metaphyseal chondrodysplasia
Nature Genetics, 1993Co-Authors: Matthew L Warman, Daniel H. Cohn, Björn Olsen, Jacqueline T. Hecht, Margaret H Abbott, Suneel S Apte, Tim Hefferon, Iain Mcintosh, Clair A FrancomanoAbstract:The expression of type X collagen is restricted to hypertrophic chondrocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the tissue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (Osteochondrodysplasias). We have identified a 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score = 18.2 at theta = 0). The mutation produces a frameshift which alters the highly conserved C-terminal domain of the alpha 1(X) chain and reduces the length of the polypeptide by nine residues. This mutation may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein.
D Trump - One of the best experts on this subject based on the ideXlab platform.
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blomstrand Osteochondrodysplasia three novel cases and histological evidence for heterogeneity
Virchows Archiv, 2000Co-Authors: Roelofjan Oostra, J J Van Der Harten, W P H A Rijnders, R J Scott, M P A Young, D TrumpAbstract:Blomstrand Osteochondrodysplasia (BOCD) is a rare, autosomal recessive, lethal skeletal dysplasia characterized by generalized osteosclerosis and advanced skeletal maturation. The histopathological characteristics of three novel cases (two isolated cases and a sib-pair) of BOCD are presented and correlated with the clinical and radiographical findings, and the relevant literature is reviewed. The results of our study confirm the existence of two separate types of BOCD, which we propose naming type I: the severe, 'classical' form, and type II: a less severe form.
