Summary: Abnormal development of cartilage and bone.

Top Publications

  1. Rider N, Morton D, Puffenberger E, Hendrickson C, Robinson D, Strauss K. Immunologic and clinical features of 25 Amish patients with RMRP 70 A-->G cartilage hair hypoplasia. Clin Immunol. 2009;131:119-28 pubmed publisher
    ..Gauging this risk is difficult, and thus careful monitoring of all patients with cartilage-hair hypoplasia is warranted...
  2. Ozbek M, Senée V, Aydemir S, Kotan L, Mungan N, Yuksel B, et al. Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. Pediatr Diabetes. 2010;11:279-85 pubmed publisher
    ..Other than the consistent features of diabetes mellitus and epiphyseal dysplasia, WRS patients are otherwise characterized by extensive phenotypic variability that correlates poorly to genotype...
  3. Loukin S, Su Z, Kung C. Increased basal activity is a key determinant in the severity of human skeletal dysplasia caused by TRPV4 mutations. PLoS ONE. 2011;6:e19533 pubmed publisher
  4. Feng D, Meng Y, Zhao S, Shi H, Wang W, Huang S. [Two novel EIF2AK3 mutations in a Chinese boy with Wolcott-Rallison syndrome]. Zhonghua Er Ke Za Zhi. 2011;49:301-5 pubmed
    ..Here we describe a Chinese boy affected by WRS. Genetic testing of his EIF2AK3 gene was performed in order to elucidate molecular variations and subsequently to provide credible genetic counseling for prenatal diagnosis in his family...
  5. Herzog A, Genin O, Hasdai A, Shinder D, Pines M. Hsp90 and angiogenesis in bone disorders--lessons from the avian growth plate. Am J Physiol Regul Integr Comp Physiol. 2011;301:R140-7 pubmed publisher
  6. Andreucci E, Aftimos S, Alcausin M, Haan E, Hunter W, Kannu P, et al. TRPV4 related skeletal dysplasias: a phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families. Orphanet J Rare Dis. 2011;6:37 pubmed publisher
    ..Recently, TRPV4 mutations have been found in patients diagnosed with these skeletal phenotypes...
  7. Dai J, Kim O, Cho T, Schmidt Rimpler M, Tonoki H, Takikawa K, et al. Novel and recurrent TRPV4 mutations and their association with distinct phenotypes within the TRPV4 dysplasia family. J Med Genet. 2010;47:704-9 pubmed publisher
    ..Only a total of seven missense mutations were detected, however. The full spectrum of TRPV4 mutations and their phenotypes remained unclear...
  8. Nundlall S, Rajpar M, Bell P, Clowes C, Zeeff L, Gardner B, et al. An unfolded protein response is the initial cellular response to the expression of mutant matrilin-3 in a mouse model of multiple epiphyseal dysplasia. Cell Stress Chaperones. 2010;15:835-49 pubmed publisher
    ..We performed similar studies with a mouse model of Schmid metaphyseal chondrodysplasia, but again this treatment did not improve the phenotype. ..
  9. Bell P, Piróg K, Fresquet M, Thornton D, Boot Handford R, Briggs M. Loss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a Matn3 V194D mutation. Arthritis Rheum. 2012;64:1529-39 pubmed publisher
    ..Mutant matrilin 3 oligomers form non-native disulfide-bonded aggregates through the misfolded A domain. ..

More Information


  1. Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari T, et al. Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia. Am J Hum Genet. 2009;84:307-15 pubmed publisher
  2. Velada I, Capela Silva F, Reis F, Pires E, Egas C, Rodrigues Santos P, et al. Expression of genes encoding extracellular matrix macromolecules and metalloproteinases in avian tibial dyschondroplasia. J Comp Pathol. 2011;145:174-86 pubmed publisher
    ..These findings suggest that the accumulation of cartilage associated with the disease may be the result of decreased proteolysis due to the down-regulation of MMPs and not to an increased production of ECM macromolecules...
  3. Nishimura G, Dai J, Lausch E, Unger S, Megarbane A, Kitoh H, et al. Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. Am J Med Genet A. 2010;152A:1443-9 pubmed publisher
  4. Ciccia A, Bredemeyer A, Sowa M, Terret M, Jallepalli P, Harper J, et al. The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart. Genes Dev. 2009;23:2415-25 pubmed publisher
    ..Thus, the symptoms of SIOD may be caused, at least in part, by defects in the cellular response to DNA replication stress...
  5. Rasaputra K, Liyanage A, Lay J, McCarthy F, Rath N. Tibial dyschondroplasia-associated proteomic changes in chicken growth plate cartilage. Avian Dis. 2010;54:1166-71 pubmed
  6. Choi M, Chan C, Chan D, Luk K, Cheah K, Tanner J. Biochemical consequences of sedlin mutations that cause spondyloepiphyseal dysplasia tarda. Biochem J. 2009;423:233-42 pubmed publisher
    ..Our results suggest that the sedlin mutations S73L, F83S and V130D cause SEDT by sedlin misfolding, whereas the D47Y mutation may influence normal TRAPP (transport protein particle) dynamics...
  7. Dan H, Simsa Maziel S, Hisdai A, Sela Donenfeld D, Monsonego Ornan E. Expression of matrix metalloproteinases during impairment and recovery of the avian growth plate. J Anim Sci. 2009;87:3544-55 pubmed publisher
    ..Our results strengthen the link between MMP expression and growth-plate impairment, and we suggest that gelatinase activity (MMP-2 and 9) facilitates this process...
  8. Smithson S, Grier D, Hall C. Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type. Clin Dysmorphol. 2009;18:31-5 pubmed publisher
    ..The occurrence of affected siblings with normal parents in three families and consanguinity on three occasions indicates autosomal recessive inheritance...
  9. Baradaran Heravi A, Cho K, Tolhuis B, Sanyal M, Morozova O, Morimoto M, et al. Penetrance of biallelic SMARCAL1 mutations is associated with environmental and genetic disturbances of gene expression. Hum Mol Genet. 2012;21:2572-87 pubmed publisher
    ..We conclude that the SMARCAL1 annealing helicase buffers fluctuations in gene expression and that alterations in gene expression contribute to the penetrance of SIOD...
  10. Cameron T, Bell K, Tatarczuch L, Mackie E, Rajpar M, McDermott B, et al. Transcriptional profiling of chondrodysplasia growth plate cartilage reveals adaptive ER-stress networks that allow survival but disrupt hypertrophy. PLoS ONE. 2011;6:e24600 pubmed publisher
    ..Thus they provide important insights into ER stress signaling and its impact on cartilage pathophysiology...
  11. Femitha P, Joy R, Gane B, Adhisivam B, Bhat B. Frank-Ter Haar syndrome in a newborn. Indian J Pediatr. 2012;79:1091-3 pubmed publisher
    ..It is usually transmitted as autosomal recessive disorder. Only a few cases have been reported in the literature and none from India. The authors report a case with other unusual features and a short review of the condition...
  12. Mihci E, Türkkahraman D, Ellard S, Akçurin S, Bircan I. Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. J Clin Res Pediatr Endocrinol. 2012;4:101-3 pubmed publisher
    ..This patient demonstrates that the other findings of this syndrome might be obscured by a diagnosis of isolated neonatal diabetes. ..
  13. Dundar M, Saatci C, Tasdemir S, Akcakus M, Caglayan A, Ozkul Y. Frank-ter Haar syndrome with unusual clinical features. Eur J Med Genet. 2009;52:247-9 pubmed publisher
    ..Hypopigmented areas in hair, bilateral adducted thumb, bilateral contractures in elbows and pelvic limb, atrial septal defect have not been described previously in the literature. Our patient also had double-outlet right ventricle...
  14. Sang Y, Liu M, Yang W, Yan J, Chengzhu -, Ni G. A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. J Pediatr Endocrinol Metab. 2011;24:181-4 pubmed
    ..In the present study, we analyzed the EIF2AK3 gene in a 10-year-old WRS patient and his parents to study the clinical features and the mechanism for genetic onset of WRS...
  15. Jackson G, Mittaz Crettol L, Taylor J, Mortier G, Spranger J, Zabel B, et al. Pseudoachondroplasia and multiple epiphyseal dysplasia: a 7-year comprehensive analysis of the known disease genes identify novel and recurrent mutations and provides an accurate assessment of their relative contribution. Hum Mutat. 2012;33:144-57 pubmed publisher
    ..Furthermore, this study provides the first indication of the relative contribution of each gene and confirms that they account for the majority of PSACH and MED. ..
  16. Krakow D, Rimoin D. The skeletal dysplasias. Genet Med. 2010;12:327-41 pubmed publisher
    The skeletal dysplasias (osteochondrodysplasias) are a heterogeneous group of more than 350 disorders frequently associated with orthopedic complications and varying degrees of dwarfism or short stature...
  17. Arboleda V, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz de Souza B, et al. Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012;44:788-92 pubmed publisher
    ..All IMAGe-associated mutations clustered in the PCNA-binding domain of CDKN1C and resulted in loss of PCNA binding, distinguishing them from the mutations of CDKN1C that cause Beckwith-Wiedemann syndrome, an overgrowth syndrome. ..
  18. Holt D, Henderson M, Stockdale C, Farrell J, Kooyman D, Bridgewater L, et al. Osteoarthritis-like changes in the heterozygous sedc mouse associated with the HtrA1-Ddr2-Mmp-13 degradative pathway: a new model of osteoarthritis. Osteoarthritis Cartilage. 2012;20:430-9 pubmed publisher
  19. Bansbach C, Betous R, Lovejoy C, Glick G, Cortez D. The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks. Genes Dev. 2009;23:2405-14 pubmed publisher
    ..Thus, SMARCAL1 is a replication stress response protein, and the pleiotropic phenotypes of SIOD are at least partly due to defects in genome maintenance during DNA replication...
  20. Ali B, Xu H, Akawi N, John A, Karuvantevida N, Langer R, et al. Trafficking defects and loss of ligand binding are the underlying causes of all reported DDR2 missense mutations found in SMED-SL patients. Hum Mol Genet. 2010;19:2239-50 pubmed publisher
    ..Our data thus demonstrate that SMED-SL can result from at least two different loss-of-function mechanisms: namely defects in DDR2 targeting to the plasma membrane or the loss of its ligand-binding activity...
  21. Jackson G, Marcus Soekarman D, Stolte Dijkstra I, Verrips A, Taylor J, Briggs M. Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy. Am J Med Genet A. 2010;152A:863-9 pubmed publisher
    ..This study therefore extends the range of gene-mutations that can cause MED-related myopathy. (c) 2010 Wiley-Liss, Inc. ..
  22. Unger S, Lausch E, Stanzial F, Gillessen Kaesbach G, Stefanova I, Di Stefano C, et al. Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy?. Am J Med Genet A. 2011;155A:2860-4 pubmed publisher
  23. Piróg K, Jaka O, Katakura Y, Meadows R, Kadler K, Boot Handford R, et al. A mouse model offers novel insights into the myopathy and tendinopathy often associated with pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Mol Genet. 2010;19:52-64 pubmed publisher
    ..This is the first comprehensive characterization of the musculoskeletal phenotype of PSACH-MED and is directly relevant to the clinical management of these patients. ..
  24. Xia X, Cui Y, Zhou Y, Zhou X, Shi Y, Wei L, et al. A novel insertion mutation in the SEDL gene results in X-linked spondyloepiphyseal dysplasia tarda in a large Chinese pedigree. Clin Chim Acta. 2009;410:39-42 pubmed publisher
    ..The objective of this study is to describe a large Chinese SEDT family with a milder phenotype and describe the molecular and clinical findings...
  25. Julier C, Nicolino M. Wolcott-Rallison syndrome. Orphanet J Rare Dis. 2010;5:29 pubmed publisher
    ..Prognosis is poor and most patients die at a young age. Intervention strategies targeting ER dysfunction provide hope for future therapy and prevention...
  26. Bargal R, Cormier Daire V, Ben Neriah Z, Le Merrer M, Sosna J, Melki J, et al. Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications. Am J Hum Genet. 2009;84:80-4 pubmed publisher
    ..The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk...
  27. Reis A, Kannengiesser C, Jennane F, Manna T, Cheurfa N, Oudin C, et al. Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. Pediatr Diabetes. 2011;12:187-91 pubmed publisher
    ..The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis...
  28. Nakashima E, Kitoh H, Maeda K, Haga N, Kosaki R, Mabuchi A, et al. Novel COL9A3 mutation in a family with multiple epiphyseal dysplasia. Am J Med Genet A. 2005;132A:181-4 pubmed
    ..The radiographic phenotypes of the patients were relatively milder than those of previously reported cases, and were indistinguishable to common, idiopathic OA. ..
  29. Deguchi K, Clewing J, Elizondo L, Hirano R, Huang C, Choi K, et al. Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1. J Neuropathol Exp Neurol. 2008;67:565-77 pubmed publisher
    ..These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation. ..
  30. Fiedler J, Stove J, Heber F, Brenner R. Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2). Am J Med Genet. 2002;112:144-53 pubmed
    ..In these patients and their families, mutation screening of the candidate regions may help to confirm the diagnosis, lead to appropriate advice for lifestyle and well based genetic counseling. ..
  31. Cohn D, Ehtesham N, Krakow D, Unger S, Shanske A, Reinker K, et al. Mental retardation and abnormal skeletal development (Dyggve-Melchior-Clausen dysplasia) due to mutations in a novel, evolutionarily conserved gene. Am J Hum Genet. 2003;72:419-28 pubmed
    ..dysplasia (DMC) and Smith-McCort dysplasia (SMC) are similar, rare autosomal recessive osteochondrodysplasias. The radiographic features and cartilage histology in DMC and SMC are identical...
  32. Borochowitz Z, Scheffer D, Adir V, Dagoneau N, Munnich A, Cormier Daire V. Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD. J Med Genet. 2004;41:366-72 pubmed
  33. Kleerekoper Q, Hecht J, Putkey J. Disease-causing mutations in cartilage oligomeric matrix protein cause an unstructured Ca2+ binding domain. J Biol Chem. 2002;277:10581-9 pubmed
    ..Persistence of an unstructured state of the mutated Ca(2+) binding domain in COMP is the structural basis for retention of COMP in the rough endoplasmic reticulum of differentiated PSACH and EDM1 chondrocytes...
  34. Chapman K, Mortier G, Chapman K, Loughlin J, Grant M, Briggs M. Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia. Nat Genet. 2001;28:393-6 pubmed
    ..These are the first mutations to be identified in any of the genes encoding the matrilin family of proteins and confirm a role for matrilin-3 in the development and homeostasis of cartilage and bone. ..
  35. Yusufzai T, Kadonaga J. HARP is an ATP-driven annealing helicase. Science. 2008;322:748-50 pubmed publisher
    ..Moreover, the pleiotropy of HARP mutations is consistent with the function of HARP as an annealing helicase that acts throughout the genome to oppose the action of DNA-unwinding activities in the nucleus. ..
  36. Mabuchi A, Haga N, Maeda K, Nakashima E, Manabe N, Hiraoka H, et al. Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia. Hum Mutat. 2004;24:439-40 pubmed
    ..120-127). Contrary to the previous assumption that the MATN3 mutation in MED is confined to the beta-sheet regions, one novel mutation (p.F105S) is located outside the beta-sheet region, within an alpha-helix region. ..
  37. Vatanavicharn N, Lachman R, Rimoin D. Multilayered patella: similar radiographic findings in pseudoachondroplasia and recessive multiple epiphyseal dysplasia. Am J Med Genet A. 2008;146A:1682-6 pubmed publisher
  38. Zankl A, Jackson G, Crettol L, Taylor J, Elles R, Mortier G, et al. Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia. Eur J Hum Genet. 2007;15:150-4 pubmed
    ..We conclude that expert clinical-radiological review can significantly enhance mutation detection rates and should be part of any diagnostic mutation screening protocol for skeletal dysplasias. ..
  39. Arikawa Hirasawa E, Le A, Nishino I, Nonaka I, Ho N, Francomano C, et al. Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia. Am J Hum Genet. 2002;70:1368-75 pubmed
    ..These findings suggest that perlecan has an important role in neuromuscular function and cartilage formation, and they define the molecular basis involved in the difference in the phenotypic severity between DDSH and SJS. ..
  40. Aszodi A, Hunziker E, Brakebusch C, Fassler R. Beta1 integrins regulate chondrocyte rotation, G1 progression, and cytokinesis. Genes Dev. 2003;17:2465-79 pubmed
    ..Altogether these findings establish that beta1-integrin-dependent motility and proliferation of chondrocytes are mandatory events for endochondral bone formation to occur. ..
  41. Hall C. International nosology and classification of constitutional disorders of bone (2001). Am J Med Genet. 2002;113:65-77 pubmed
    ..For these reasons a further update on the classification is appropriate. It has been expended to not only the osteochondrodysplasias (33 groups) but also genetically determined dysostoses (3 groups).
  42. Renella R, Schaefer E, LeMerrer M, Alanay Y, Kandemir N, Eich G, et al. Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. Am J Med Genet A. 2006;140:541-50 pubmed
    ..The notion of recessive inheritance hitherto assumed is challenged by the observation of two apparently dominant pedigrees. ..
  43. Czarny Ratajczak M, Lohiniva J, Rogala P, Kozlowski K, Perala M, Carter L, et al. A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity. Am J Hum Genet. 2001;69:969-80 pubmed
    ..The results show that mutations in COL9A1 can cause MED, but they also suggest that mutations in COL9A1, COL9A2, COL9A3, COMP, and DTDST are not the major causes of MED and that there exists at least one additional locus. ..
  44. Hoogendam J, Farih Sips H, Wÿnaendts L, Lowik C, Wit J, Karperien M. Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteochondrodysplasia types I and II. J Clin Endocrinol Metab. 2007;92:1088-95 pubmed
  45. Jakkula E, Lohiniva J, Capone A, Bonafe L, Marti M, Schuster V, et al. A recurrent R718W mutation in COMP results in multiple epiphyseal dysplasia with mild myopathy: clinical and pathogenetic overlap with collagen IX mutations. J Med Genet. 2003;40:942-8 pubmed
  46. Senée V, Vattem K, Delepine M, Rainbow L, Haton C, Lecoq A, et al. Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. Diabetes. 2004;53:1876-83 pubmed
  47. Menezes A. Specific entities affecting the craniocervical region: osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management of basilar impression. Childs Nerv Syst. 2008;24:1169-72 pubmed publisher
    ..Osteogenesis imperfecta (OI) is an inheritable disorder of bone development caused by defective collagen synthesis. The attendant basilar impression or secondary basilar invagination is uncommon but can be devastating...
  48. Mabuchi A, Manabe N, Haga N, Kitoh H, Ikeda T, Kawaji H, et al. Novel types of COMP mutations and genotype-phenotype association in pseudoachondroplasia and multiple epiphyseal dysplasia. Hum Genet. 2003;112:84-90 pubmed
    ..0024). These findings expand the mutation spectrum of the COMP gene and highlight genotype-phenotype relationships, facilitating improved genetic diagnosis and analysis of COMP function in humans...
  49. Paupe V, Gilbert T, Le Merrer M, Munnich A, Cormier Daire V, El Ghouzzi V. Recent advances in Dyggve-Melchior-Clausen syndrome. Mol Genet Metab. 2004;83:51-9 pubmed
    ..The present review focuses on clinical, radiological, and cellular features and evolution of DMC/SMC syndromes and discusses them with regard to identified Dym mutations and possible roles of the Dym gene product...
  50. Clewing J, Fryssira H, Goodman D, Smithson S, Sloan E, Lou S, et al. Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2007;28:273-83 pubmed
    ..This is the first evidence for nonallelic heterogeneity in SIOD. From analysis of the postmortem histopathology from two patients and the clinical data from most patients, we propose the existence of endophenotypes of SIOD...
  51. Takeuchi H, Ito K, Ogino T, Hasegawa T, Kitamura M, Ishii S. A case of osteocartilaginous mass involving the coronoid process of the ulna: solitary osteochondroma or dysplasia epiphysealis hemimelica?. J Shoulder Elbow Surg. 2003;12:510-3 pubmed
  52. de Wit M, de Coo I, Julier C, Delepine M, Lequin M, van de Laar I, et al. Microcephaly and simplified gyral pattern of the brain associated with early onset insulin-dependent diabetes mellitus. Neurogenetics. 2006;7:259-63 pubmed
    ..Our findings suggest that in some cases, early onset IDDM and SGP can arise from common mechanisms leading to increased apoptosis...
  53. Krakow D, Alanay Y, Rimoin L, Lin V, Wilcox W, Lachman R, et al. Evaluation of prenatal-onset osteochondrodysplasias by ultrasonography: a retrospective and prospective analysis. Am J Med Genet A. 2008;146A:1917-24 pubmed publisher
    The osteochondrodysplasias or skeletal dysplasias are a heterogenous group of over 350 distinct disorders of skeletogenesis. Many manifest in the prenatal period, making them amenable to ultrasound prenatal diagnosis...
  54. Iyer S, Korada M, Rainbow L, Kirk J, Brown R, Shaw N, et al. Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. Acta Paediatr. 2004;93:1195-201 pubmed
    ..So far, 17 children have been described in the world literature. Recently, mutations in the gene encoding EIF2AK3 have been shown to segregate with the syndrome in three affected families...
  55. Ballhausen D, Bonafe L, Terhal P, Unger S, Bellus G, Classen M, et al. Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W. J Med Genet. 2003;40:65-71 pubmed
  56. Unger S, Bonafe L, Superti Furga A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol. 2008;22:19-32 pubmed publisher
    ..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...
  57. Newman B, Wallis G. Skeletal dysplasias caused by a disruption of skeletal patterning and endochondral ossification. Clin Genet. 2003;63:241-51 pubmed
    ..This review considers how some of the recent advances in human and murine genetics have led to an increased understanding of normal bone development and, in particular, the processes of skeletal patterning and endochondral ossification...
  58. Chen T, Posey K, Hecht J, Vertel B. COMP mutations: domain-dependent relationship between abnormal chondrocyte trafficking and clinical PSACH and MED phenotypes. J Cell Biochem. 2008;103:778-87 pubmed
    ..These findings suggest that other unidentified factors contribute to the effect of the CTD mutations. J. Cell. Biochem. 103: 778-787, 2008. (c) 2007 Wiley-Liss, Inc...
  59. Tuysuz B, Gazioglu N, Ungür S, Aji D, Turkmen S. The time of onset of abnormal calcification in spondylometaepiphyseal dysplasia, short limb-abnormal calcification type. Pediatr Radiol. 2009;39:84-9 pubmed publisher
    ..When abnormal calcifications are not yet present, but radiological changes associated with SMED are present, this rare disease must be considered...
  60. Hecht J, Hayes E, Snuggs M, Decker G, Montufar Solis D, Doege K, et al. Calreticulin, PDI, Grp94 and BiP chaperone proteins are associated with retained COMP in pseudoachondroplasia chondrocytes. Matrix Biol. 2001;20:251-62 pubmed
    ..These results suggest that these proteins play a role in the processing and transport of wild type COMP in normal chondrocytes and in the retention of mutant COMP in PSACH chondrocytes...
  61. Stelzer C, Winterpacht A, Spranger J, Zabel B. Grebe dysplasia and the spectrum of CDMP1 mutations. Pediatr Pathol Mol Med. 2003;22:77-85 pubmed
    ..A dominant negative action on other bone morphogenetic proteins is unlikely to cause the severe disruption of skeletogenesis seen in this case of Grebe dysplasia...
  62. Ridanpää M, Jain P, McKusick V, Francomano C, Kaitila I. The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases. Am J Med Genet C Semin Med Genet. 2003;121C:81-3 pubmed
    ..1965: Bull Johns Hopkins Hosp 116:231-272]...
  63. Makitie O, Mortier G, Czarny Ratajczak M, Wright M, Suri M, Rogala P, et al. Clinical and radiographic findings in multiple epiphyseal dysplasia caused by MATN3 mutations: description of 12 patients. Am J Med Genet A. 2004;125A:278-84 pubmed
    ..Despite overlap, both clinically and radiographically, with other forms of MED, the described features may help to differentiate this particular form from other entities within the MED spectrum...
  64. Nakashima E, Ikegawa S, Ohashi H, Kimizuka M, Nishimura G. Double-layered patella in multiple epiphyseal dysplasia is not exclusive to DTDST mutation. Am J Med Genet A. 2005;133A:106-7 pubmed
  65. Cotterill S, Jackson G, Leighton M, Wagener R, Makitie O, Cole W, et al. Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3. Hum Mutat. 2005;26:557-65 pubmed
    ..In summary, the data presented in this paper suggest that MED caused by MATN3 mutations is the result of an intracellular retention of the mutant protein...
  66. Takahashi M, Matsui Y, Goto T, Nishimura G, Ikegawa S, Ohashi H, et al. Intrafamilial phenotypic diversity in multiple epiphyseal dysplasia associated with a COL9A2 mutation (EDM2). Clin Rheumatol. 2006;25:591-5 pubmed
  67. Spitznagel L, Nitsche D, Paulsson M, Maurer P, Zaucke F. Characterization of a pseudoachondroplasia-associated mutation (His587-->Arg) in the C-terminal, collagen-binding domain of cartilage oligomeric matrix protein (COMP). Biochem J. 2004;377:479-87 pubmed
    ..Our results suggest that the His(587)-->Arg mutation is not itself deleterious to the structure and collagen-binding of COMP...
  68. Posey K, Hayes E, Haynes R, Hecht J. Role of TSP-5/COMP in pseudoachondroplasia. Int J Biochem Cell Biol. 2004;36:1005-12 pubmed
    ..Gene therapy will need to target the reduction of COMP in order to restore normal chondrocyte function and longevity...
  69. Fiedler J, Le Merrer M, Mortier G, Heuertz S, Faivre L, Brenner R. X-linked spondyloepiphyseal dysplasia tarda: Novel and recurrent mutations in 13 European families. Hum Mutat. 2004;24:103 pubmed
    ..All sequence variations identified are either deletions of complete exons or predicted to result in a premature stop codon or to lead into splicing defects and are associated with a loss of considerable parts of the sedlin protein...
  70. Unger S, Hecht J. Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. Am J Med Genet. 2001;106:244-50 pubmed
    ..PSACH) (OMIM#177170) and multiple epiphyseal dysplasia (MED) are separate but overlapping osteochondrodysplasias. PSACH is a dominantly inherited disorder characterized by short-limb short stature, loose joints, and ..
  71. Kavadas F, Giliani S, Gu Y, Mazzolari E, Bates A, Pegoiani E, et al. Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J Allergy Clin Immunol. 2008;122:1178-84 pubmed publisher
    ..Typical features of cartilage hair hypoplasia include short stature, a predisposition to malignancy, and a variable degree of impairment of cellular immunity...
  72. Dias C, Cairns R, Patel M. Sudden death in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type. Clin Dysmorphol. 2009;18:25-9 pubmed publisher
    ..SMED SL-AC should be added to the list of genetic causes of sudden death. Radiological features in the hand may be used in the first few years of life to support an early diagnosis and thus allow for prevention of premature demise...