The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
David L. Rimoin - One of the best experts on this subject based on the ideXlab platform.
-
Multilayered patella: similar radiographic findings in pseudoachondroplasia and recessive Multiple Epiphyseal Dysplasia.
American journal of medical genetics. Part A, 2008Co-Authors: Nithiwat Vatanavicharn, Ralph S. Lachman, David L. RimoinAbstract:A multilayered patella is a characteristic radiographic finding of recessive Multiple Epiphyseal Dysplasia (rMED) caused by DTDST mutations. However it has been recently reported in a dominant MED case with a COL9A2 mutation. We report on a new radiographic patellar finding in a patient with pseudoachondroplasia and a heterozygous COMP mutation. It is similar to the radiographic appearance of fusing multilayered patellae in rMED cases. This led us to search the International Skeletal Dysplasia Registry for similar abnormalities. We did not observe this finding in other skeletal Dysplasias or other pseudoachondroplasia cases. However we found an accessory ossification center of the patella in another pseudoachondroplasia case. Thus, we hypothesize that variable defects of cartilage extracellular matrix can result in similar abnormal patellar ossifications, and emphasize the importance of a lateral knee radiograph in patients with the pseudoachondroplasia-MED bone Dysplasia group of disorders.
-
MED, COMP, multilayered and NEIN: an overview of Multiple Epiphyseal Dysplasia
Pediatric Radiology, 2005Co-Authors: Ralph S. Lachman, Daniel H. Cohn, Deborah Krakow, David L. RimoinAbstract:This overview covers the group of disorders that presents radiographically as Multiple Epiphyseal Dysplasia (MED). The disorders include “classic MED” (Ribbing and Fairbank types): MED that is caused by mutations in the cartilage oligomeric matrix protein ( COMP ), type IX collagen , and matrilin 3 genes ( MATN3 ); and MED with multilayered patella, brachydactyly , and clubbed feet resultant from mutations in gene defect diastrophic Dysplasia ( DTDST ) . The recently identified gene/molecular abnormalities in these disorders have made more exact identification possible in many cases, al though clinical testing is not always available. However, there are specific radiographic findings that allow the accurate diagnosis to be made, thus potentially guiding which molecular defect(s) should be investigated. The modes of inheritance of these distinct MED conditions are not identical. When a specific diagnosis is made, proper genetic counseling as well as prognostication, management issues and complications can be delineated to the patient and family. This review will include the mechanics of diagnostic and molecular triage for these disorders.
-
Multiple Epiphyseal Dysplasia: radiographic abnormalities correlated with genotype.
Pediatric radiology, 2001Co-Authors: Sheila Unger, Leena Ala-kokko, Petteri Paassilta, Jaana Lohiniva, Michael D. Briggs, Ralph S. Lachman, David L. Rimoin, Paul Holden, Bernhard Zabel, Daniel H. CohnAbstract:Multiple Epiphyseal Dysplasia (MED) is an osteochondroDysplasia characterized clinically by mild short stature and early-onset degenerative joint disease and radiographically by Epiphyseal hypoplasia/Dysplasia. MED is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three genes: the cartilage oligomeric matrix protein (COMP) gene (EDM1) and the COL9A2 (EDM2) and COL9A3 (EDM3) genes of type IX procollagen. We present here a comparison of the radiographic phenotypes of MED patients with type IX collagen gene mutations and those with COMP gene mutations. We reviewed radiographs from two patients with MED produced by COMP mutations, two families with COL9A2 mutations, and one family with a mutation in COL9A3. The data demonstrated that the patients with type IX collagen defects had more severe joint involvement at the knees and relative hip sparing, while the patients with COMP mutations had significant involvement at the capital femoral epiphyses and irregular acetabuli. This pattern of joint involvement was consistent regardless of overall degree of severity of the phenotype.
-
Pseudoachondroplasia and Multiple Epiphyseal Dysplasia due to mutations in the cartilage oligomeric matrix protein gene
Nature genetics, 1995Co-Authors: Briggs, David L. Rimoin, Susan M.g. Hoffman, Lily King, Anne S. Olsen, Harvey W. Mohrenweiser, Jules G. Leroy, Geert Mortier, Ralph S. LachmanAbstract:Pseudoachondroplasia (PSACH) and Multiple Epiphyseal Dysplasia (MED) are dominantly inherited chondroDysplasias characterized by short stature and early-onset osteoarthrosis. The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. In three patients with these diseases, we identified COMP mutations in a region of the gene that encodes a Ca++ binding motif. Our data demonstrate that PSACH and some forms of MED are allelic and suggest an essential role for Ca++ binding in COMP structure and function.
-
A large family with features of pseudoachondroplasia and Multiple Epiphyseal Dysplasia: exclusion of seven candidate gene loci that encode proteins of the cartilage extracellular matrix
Human Genetics, 1994Co-Authors: David L. Rimoin, Michael D. Briggs, Matthew L. Warman, I. Merete Rasmussen, Peter J. Roughley, Helen E. Gruber, Bjorn R. Olsen, Y. Edward Hsia, Juliet Yuen, Kent ReinkerAbstract:We have identified a large family with a dominantly inherited chondroDysplasia characterized by a waddling gait, short limbs, and early onset osteoarthritis. The radiographic presentation resembles pseudoachondroplasia in childhood and Multiple Epiphyseal Dysplasia in adults. Electron microscopic examination of cartilage reveals accumulation of material within the rough endoplasmic reticulum similar to that seen in pseudoachondroplasia and the Fairbank type of Multiple Epiphyseal Dysplasia. By linkage analysis, we have excluded the genes for aggrecan, decorin, hexabrachion (tenascin), type II procollagen, the α1 chain of type XI procollagen, the α1 chain of type IX procollagen, and link protein, candidate genes that encode structural components of the cartilage extracellular matrix, as the disease locus for this disorder.
Andrea Superti-furga - One of the best experts on this subject based on the ideXlab platform.
-
Multiple Epiphyseal Dysplasia: clinical and radiographic features, differential diagnosis and molecular basis
Best practice & research. Clinical rheumatology, 2008Co-Authors: Sheila Unger, Luisa Bonafé, Andrea Superti-furgaAbstract:Multiple Epiphyseal Dysplasia is one of the more common skeletal Dysplasias but it can still be difficult to diagnose. The presenting signs are often rheumatological ('joint pain') or neurological ('myopathy') in nature, and the cardinal feature of skeletal Dysplasia (short stature) may not be present. A radiographic skeletal survey is necessary to delineate the pattern of generalized delayed Epiphyseal ossification and changes in Epiphyseal contour. Once the diagnosis of Multiple Epiphyseal Dysplasia has been established, careful examination of the radiographs can help to determine which genes should be analysed. Mutations in at least six different genes can cause Multiple Epiphyseal Dysplasia, and it can be either dominant or recessive. Molecular diagnosis is important for accurate prognosis and genetic counselling.
-
Recessively inherited Multiple Epiphyseal Dysplasia with normal stature, club foot, and double layered patella caused by a DTDST mutation.
Journal of medical genetics, 1999Co-Authors: Andrea Superti-furga, Luitgard M. Neumann, Thomas Riebel, Georg Eich, Beat Steinmann, Jürgen W. Spranger, Jürgen KunzeAbstract:We have observed over 25 different mutations in the diastrophic Dysplasia sulphate transporter gene (DTDST) in association with the recessive disorders achondrogenesis 1B, atelosteogenesis 2, and diastrophic Dysplasia. The c862t (R279W) transition is the most common mutation in non-Finnish patients, but in these disorders it is usually combined with other DTDST mutations. We had not seen a case of homozygosity for c862t (R279W) until we analysed DNA from a 36 year old male with tall-normal stature (180 cm) who asked for genetic counselling for suspected Multiple Epiphyseal Dysplasia. He was treated for club foot and hip Dysplasia at birth. Skeletal changes consistent with Multiple Epiphyseal Dysplasia, with the peculiar finding of a double layered patella, were recognised during childhood. Cleft palate, swelling of the ear pinna, and hitch hiker thumb were absent. He was found to be homozygous, and both healthy parents heterozygous, for the R279W mutation in DTDST, and his fibroblasts showed a sulphate incorporation defect typical of DTDST disorders. Counselling was given for a recessive disorder, thereby considerably reducing the probability of affected offspring. Multiple Epiphyseal Dysplasia is more frequently caused by dominant mutations in the COMP (EDM1, McKusick 132400) and COL9A2 genes (EDM2, McKusick 600204). A few other patients and families with features similar to our proband have been described previously and considered to have autosomal recessive MED (EDM4, McKusick 226900). This observation confirms the existence of this entity and assigns it to the phenotypic spectrum associated with mutations at the DTDST locus.
Michael D. Briggs - One of the best experts on this subject based on the ideXlab platform.
-
Multiple Epiphyseal Dysplasia, Autosomal Dominant
2015Co-Authors: Michael D. Briggs, Michael Wright, Geert MortierAbstract:Clinical characteristics Autosomal dominant Multiple Epiphyseal Dysplasia (MED) presents in early childhood, usually with pain in the hips and/or knees after exercise. Affected children complain of fatigue with long-distance walking. Waddling gait may be present. Adult height is either in the lower range of normal or mildly shortened. The limbs are relatively short in comparison to the trunk. Pain and joint deformity progress, resulting in early-onset osteoarthritis, particularly of the large weight-bearing joints. Diagnosis/testing The diagnosis of autosomal dominant MED is established in a proband with the typical clinical and radiographic findings and/or a heterozygous pathogenic variant in COL9A1, COL9A2, COL9A3, COMP, or MATN3 identified by molecular genetic testing. Management Treatment of manifestations: For pain control, a combination of analgesics and physiotherapy including hydrotherapy; referral to a rheumatologist or pain specialist as needed; consideration of realignment osteotomy and/or acetabular osteotomy to limit joint destruction and development of osteoarthritis. Consider total joint arthroplasty if the degenerative hip changes cause uncontrollable pain/dysfunction; offer psychosocial support addressing issues of short stature, chronic pain, disability, and employment. Surveillance: Evaluation by an orthopedic surgeon for chronic pain and/or limb deformities (genu varum, genu valgum). Agents/circumstances to avoid: Obesity; exercise causing repetitive strain on affected joints. Genetic counseling Many individuals with autosomal dominant MED have inherited the pathogenic variant from a parent. The prevalence of de novo pathogenic variants is not known. Each child of an individual with autosomal dominant MED has a 50% chance of inheriting the pathogenic variant. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for autosomal dominant Multiple Epiphyseal Dysplasia are possible if the pathogenic variant has been identified in an affected family member.
-
RESEARCH ARTICLE Type IX Collagen Gene Mutations Can Result in Multiple Epiphyseal Dysplasia That Is Associated With
2009Co-Authors: Osteochondritis Dissecans, Aad Verrips, Mild A Myopathy, Gail C. Jackson, Dominique Marcus-soekarman, Irene Stolte-dijkstra, Jacqueline A. Taylor, Michael D. BriggsAbstract:Multiple Epiphyseal Dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal domi-nant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix protein, and matrilin-3: COL9A1, COL9A2, COL9A3, COMP, and MATN3, respectively. Splicing mutations have been identified in all three genes encod-ing type IX collagen and are restricted to specific exons encoding an equivalent region of the COL3 domain in all three a(IX) chains. MED has been associated with mild myopathy in some families, in particular one family with a COL9A3 mutation and two families with C-terminal COMP mutations. In this study we have identified COL9A2 mutations in two families with MED that also have osteochondritis dissecans and mild myopathy. This study therefore extends the range of gene-mutations that can cause MED-related myopathy. 2010 Wiley-Liss, Inc. Key words: Multiple Epiphyseal Dysplasia; myopthathy; type IX collagen; cartilage; osteochondritis dissecan
-
Review: clinical variability and genetic heterogeneity in Multiple Epiphyseal Dysplasia.
Pediatric pathology & molecular medicine, 2003Co-Authors: K Chapman, Michael D. Briggs, Geert MortierAbstract:This review reports on Multiple Epiphyseal Dysplasia (MED), first described clinically in the early part of the 20th century. Over 50 years later, we are now beginning to unravel the mystery behind the genetic mutations involved in triggering the changes in cartilage observed in this condition. In the past decade considerable progress has been made in identifying the underlying genetic defect in some forms of MED. Understanding the precise effect that these molecular changes have on the integrity of the cartilage extracellular matrix will lead the way in identifying the complex disease pathophysiology that defines MED. In addition, a greater understanding of the role and interactions of specific cartilage molecules may reveal the basis of more widespread cartilage disorders such as osteoarthritis.
-
Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: Mutation review, molecular interactions, and genotype to phenotype correlations
Human mutation, 2002Co-Authors: Michael D. Briggs, K ChapmanAbstract:Pseudoachondroplasia (PSACH) and Multiple Epiphyseal Dysplasia (MED) constitute a bone Dysplasia family, which is both genetically and phenotypically heterogeneous. The disease spectrum ranges from mild MED, which manifests with pain and stiffness in the joints and delayed and irregular ossification of the epiphyses, to the more severe PSACH, which is characterized by marked short stature, deformity of the legs, and ligamentous laxity. PSACH is almost exclusively caused by mutations in cartilage oligomeric matrix protein (COMP) whereas various forms of MED are caused by mutations in the genes encoding COMP, type IX collagen (COL9A1, COL9A2, and COL9A3), matrilin-3 (MATN3), and solute carrier member 26, member 2 gene (SLC26A2). In this review we discuss specific disease-causing mutations and the clustering of these mutations in functionally and structurally important regions of the respective gene products, genotype to phenotype correlations, and the diagnostic relevance of mutation screening in these osteochondroDysplasias.
-
Multiple Epiphyseal Dysplasia: radiographic abnormalities correlated with genotype.
Pediatric radiology, 2001Co-Authors: Sheila Unger, Leena Ala-kokko, Petteri Paassilta, Jaana Lohiniva, Michael D. Briggs, Ralph S. Lachman, David L. Rimoin, Paul Holden, Bernhard Zabel, Daniel H. CohnAbstract:Multiple Epiphyseal Dysplasia (MED) is an osteochondroDysplasia characterized clinically by mild short stature and early-onset degenerative joint disease and radiographically by Epiphyseal hypoplasia/Dysplasia. MED is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three genes: the cartilage oligomeric matrix protein (COMP) gene (EDM1) and the COL9A2 (EDM2) and COL9A3 (EDM3) genes of type IX procollagen. We present here a comparison of the radiographic phenotypes of MED patients with type IX collagen gene mutations and those with COMP gene mutations. We reviewed radiographs from two patients with MED produced by COMP mutations, two families with COL9A2 mutations, and one family with a mutation in COL9A3. The data demonstrated that the patients with type IX collagen defects had more severe joint involvement at the knees and relative hip sparing, while the patients with COMP mutations had significant involvement at the capital femoral epiphyses and irregular acetabuli. This pattern of joint involvement was consistent regardless of overall degree of severity of the phenotype.
Shiro Ikegawa - One of the best experts on this subject based on the ideXlab platform.
-
Comprehensive screening of Multiple Epiphyseal Dysplasia mutations in Japanese population.
American journal of medical genetics. Part A, 2006Co-Authors: Taichi Itoh, Nishimura, Shuya Shirahama, Eiji Nakashima, Koichi Maeda, Nobuhiko Haga, Hiroshi Kitoh, Rika Kosaki, Hirofumi Ohashi, Shiro IkegawaAbstract:Multiple Epiphyseal Dysplasia (MED) is among the most genetically heterogeneous skeletal Dysplasias. Six genes involved in MED, COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST have been identified; however, the presence of additional disease genes has been reported, and the detection rate for mutations in known genes accounts for no more than 50% of patients with MED in Western populations. Here, we screened the six known disease genes in 35 consecutive Japanese MED patients. We analyzed the entire coding region of each gene, along with flanking intron–exon junctions, by direct sequencing. A total of 19 mutations were identified in COMP, MATN3, COL9A2, COL9A3, and DTDST. The detection rate for known mutations was higher in this study than in previous reports, and we identified a substantially different spectrum of mutations. Mutations in MATN3 were more prevalent among these Japanese patients, whereas no DTDST mutations were detected. Most of the mutations were localized within specific regions of each gene: COMP mutations were found in the calmodulin-like repeat domains; MATN3 mutations in the von Willebrand factor type A domain; and type IX collagen gene mutations occurred in the third collagenous domains. Based on the integration of clinical and genetic information, we propose an algorithm for detecting mutations in Japanese MED patients. Our study further supports the existence of additional MED gene(s). © 2006 Wiley-Liss, Inc.
-
Intrafamilial phenotypic diversity in Multiple Epiphyseal Dysplasia associated with a COL9A2 mutation (EDM2).
Clinical rheumatology, 2006Co-Authors: Mitsuhiko Takahashi, Nishimura, Shiro Ikegawa, Hirofumi Ohashi, Yoshito Matsui, Tomohiro Goto, Natsuo YasuiAbstract:We describe a Japanese family with an autosomal dominant Multiple Epiphyseal Dysplasia (MED EDM2) showing significant phenotypic diversity among the five affected members. Genomic analysis for COL9A2 identified an Ex3-1A>G heterozygous mutation, which has been proved to result in skipping of exon 3. The proband was a 9-year-old boy, who presented with ulnar club hands due to severe Epiphyseal Dysplasia in the distal ulnae. Radiological examination showed Multiple Epiphyseal Dysplasias, predominantly involving the knee and the wrist. The hip appeared almost normal. The malalignment of the wrist was successfully treated with a limb lengthening procedure. The phenotype of the asymptomatic 12-year-old brother was similar to, but milder than, that of the proband. The asymptomatic 39-year-old mother, the 35-year-old uncle, and the 65-year-old grandmother with bilateral painful knees showed radiographically mild and severe osteoarthritis of the knee, respectively, and none of them had wrist deformity.
-
Novel COL9A3 mutation in a family with Multiple Epiphyseal Dysplasia.
American journal of medical genetics. Part A, 2005Co-Authors: Eiji Nakashima, Gen Nishimura, Koichi Maeda, Nobuhiko Haga, Hiroshi Kitoh, Rika Kosaki, Hirofumi Ohashi, Akihiko Mabuchi, Shiro IkegawaAbstract:Multiple Epiphyseal Dysplasia (MED) is a common skeletal Dysplasia characterized by mild to moderate short stature, early-onset of osteoarthritis (OA) mainly in the hip and knee joints, and abnormally small and/or irregular epiphyses. MED is clinically and genetically heterogeneous. Six causative genes of MED have been reported, including type IX collagen genes (COL9A1, COL9A2, COL9A3). All the type IX collagen mutations previously reported cause exon skipping that loses the COL3 domain. Here we have identified a novel COL9A3 mutation co-segregating in a three-generation family with MED. The mutation (IVS3 + 5G > A) was speculated to lose the COL3 domain by skipping of exon 3, which was confirmed by in vitro analysis. The patients were of normal height and had minimal complaints with phenotypes being more severe in male patients. The radiographic phenotypes of the patients were relatively milder than those of previously reported cases, and were indistinguishable to common, idiopathic OA.
-
Novel COL9A3 mutation in a family with Multiple Epiphyseal Dysplasia.
American Journal of Medical Genetics Part A, 2004Co-Authors: Eiji Nakashima, Nishimura, Koichi Maeda, Nobuhiko Haga, Hiroshi Kitoh, Rika Kosaki, Hirofumi Ohashi, Akihiko Mabuchi, Shiro IkegawaAbstract:Multiple Epiphyseal Dysplasia (MED) is a common skeletal Dysplasia characterized by mild to moderate short stature, early-onset of osteoarthritis (OA) mainly in the hip and knee joints, and abnormally small and/or irregular epiphyses. MED is clinically and genetically heterogeneous. Six causative genes of MED have been reported, including type IX collagen genes (COL9A1, COL9A2, COL9A3). All the type IX collagen mutations previously reported cause exon skipping that loses the COL3 domain. Here we have identified a novel COL9A3 mutation co-segregating in a three-generation family with MED. The mutation (IVS3 + 5G > A) was speculated to lose the COL3 domain by skipping of exon 3, which was confirmed by in vitro analysis. The patients were of normal height and had minimal complaints with phenotypes being more severe in male patients. The radiographic phenotypes of the patients were relatively milder than those of previously reported cases, and were indistinguishable to common, idiopathic OA. © 2004 Wiley-Liss, Inc.
-
Stature and severity in Multiple Epiphyseal Dysplasia
Journal of pediatric orthopedics, 1998Co-Authors: Nobuhiko Haga, Shiro Ikegawa, Kozo Nakamura, Kazuharu Takikawa, Noriyo Manabe, Mamori KimizukaAbstract:We investigated the stature and radiological findings in 15 patients with Multiple Epiphyseal Dysplasia (MED). They were divided into normal-stature and short-stature groups according to their body height after 4 or 5 years of age. Their stature was not related to the involvement of the spine or epiphyses of long tubular bones except for the distal radius. Proximal phalanges and metacarpi were shorter in the short-stature group than in the normal-stature group, indicating that stature in MED had some relationship to the involvement of the wrist and hand. However, some patients in the normal-stature group showed involvement of distal radial epiphyses, and some patients in the short-stature group did not have stubby fingers. There are thus no clear-cut criteria to differentiate between the severe Fairbank type and the milder Ribbing type of MED.
Ralph S. Lachman - One of the best experts on this subject based on the ideXlab platform.
-
Multilayered patella: similar radiographic findings in pseudoachondroplasia and recessive Multiple Epiphyseal Dysplasia.
American journal of medical genetics. Part A, 2008Co-Authors: Nithiwat Vatanavicharn, Ralph S. Lachman, David L. RimoinAbstract:A multilayered patella is a characteristic radiographic finding of recessive Multiple Epiphyseal Dysplasia (rMED) caused by DTDST mutations. However it has been recently reported in a dominant MED case with a COL9A2 mutation. We report on a new radiographic patellar finding in a patient with pseudoachondroplasia and a heterozygous COMP mutation. It is similar to the radiographic appearance of fusing multilayered patellae in rMED cases. This led us to search the International Skeletal Dysplasia Registry for similar abnormalities. We did not observe this finding in other skeletal Dysplasias or other pseudoachondroplasia cases. However we found an accessory ossification center of the patella in another pseudoachondroplasia case. Thus, we hypothesize that variable defects of cartilage extracellular matrix can result in similar abnormal patellar ossifications, and emphasize the importance of a lateral knee radiograph in patients with the pseudoachondroplasia-MED bone Dysplasia group of disorders.
-
MED, COMP, multilayered and NEIN: an overview of Multiple Epiphyseal Dysplasia
Pediatric Radiology, 2005Co-Authors: Ralph S. Lachman, Daniel H. Cohn, Deborah Krakow, David L. RimoinAbstract:This overview covers the group of disorders that presents radiographically as Multiple Epiphyseal Dysplasia (MED). The disorders include “classic MED” (Ribbing and Fairbank types): MED that is caused by mutations in the cartilage oligomeric matrix protein ( COMP ), type IX collagen , and matrilin 3 genes ( MATN3 ); and MED with multilayered patella, brachydactyly , and clubbed feet resultant from mutations in gene defect diastrophic Dysplasia ( DTDST ) . The recently identified gene/molecular abnormalities in these disorders have made more exact identification possible in many cases, al though clinical testing is not always available. However, there are specific radiographic findings that allow the accurate diagnosis to be made, thus potentially guiding which molecular defect(s) should be investigated. The modes of inheritance of these distinct MED conditions are not identical. When a specific diagnosis is made, proper genetic counseling as well as prognostication, management issues and complications can be delineated to the patient and family. This review will include the mechanics of diagnostic and molecular triage for these disorders.
-
Multiple Epiphyseal Dysplasia: radiographic abnormalities correlated with genotype.
Pediatric radiology, 2001Co-Authors: Sheila Unger, Leena Ala-kokko, Petteri Paassilta, Jaana Lohiniva, Michael D. Briggs, Ralph S. Lachman, David L. Rimoin, Paul Holden, Bernhard Zabel, Daniel H. CohnAbstract:Multiple Epiphyseal Dysplasia (MED) is an osteochondroDysplasia characterized clinically by mild short stature and early-onset degenerative joint disease and radiographically by Epiphyseal hypoplasia/Dysplasia. MED is genetically heterogeneous, with autosomal dominant cases resulting from mutations in at least three genes: the cartilage oligomeric matrix protein (COMP) gene (EDM1) and the COL9A2 (EDM2) and COL9A3 (EDM3) genes of type IX procollagen. We present here a comparison of the radiographic phenotypes of MED patients with type IX collagen gene mutations and those with COMP gene mutations. We reviewed radiographs from two patients with MED produced by COMP mutations, two families with COL9A2 mutations, and one family with a mutation in COL9A3. The data demonstrated that the patients with type IX collagen defects had more severe joint involvement at the knees and relative hip sparing, while the patients with COMP mutations had significant involvement at the capital femoral epiphyses and irregular acetabuli. This pattern of joint involvement was consistent regardless of overall degree of severity of the phenotype.
-
Pseudoachondroplasia and Multiple Epiphyseal Dysplasia due to mutations in the cartilage oligomeric matrix protein gene
Nature genetics, 1995Co-Authors: Briggs, David L. Rimoin, Susan M.g. Hoffman, Lily King, Anne S. Olsen, Harvey W. Mohrenweiser, Jules G. Leroy, Geert Mortier, Ralph S. LachmanAbstract:Pseudoachondroplasia (PSACH) and Multiple Epiphyseal Dysplasia (MED) are dominantly inherited chondroDysplasias characterized by short stature and early-onset osteoarthrosis. The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. In three patients with these diseases, we identified COMP mutations in a region of the gene that encodes a Ca++ binding motif. Our data demonstrate that PSACH and some forms of MED are allelic and suggest an essential role for Ca++ binding in COMP structure and function.