Disease relevance of Osteochondrodysplasias

• Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities [1].
• A recombinant system was used to prepare human type II procollagen containing the substitution of Cys for Arg at alpha1-519 found in three unrelated families with early onset generalized osteoarthritis together with features of a mild chondrodysplasia probably best classified as spondyloepiphyseal dysplasia [2].
• Pseudotibiotalar slant is a positioning artifact which duplicates a finding recently reported as a new observation in the ankles of patients with sickel cell anemia and the configuration of tibiotalar slant described in juvenile rheumatoid arthritis, hemophilia, and multiple epiphyseal dysplasia [3].
• Shortening of the carpus occurs in multiple epiphyseal dysplasia, the otopalatodigital syndromes, Turner syndrome, arthrogryposis, and in juvenile rheumatoid arthritis [4].
• Osteodysplasty (Melnick-Needles syndrome, MNS), a severe bone dysplasia with presumed autosomal dominant inheritance, has now been described in 24 individuals, with a predominance of females (21:3) [5].

Psychiatry related information on Osteochondrodysplasias

• We report on four Japanese sibs (three brothers and one sister) with a previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation [6].

High impact information on Osteochondrodysplasias

• Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency [7].
• Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia [8].
• Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda [9].
• A mutation in the gene encoding the alpha 2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2) [10].
• Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus [11].

Chemical compound and disease context of Osteochondrodysplasias

• Low basal transcription of genes for tissue-specific collagens by fibroblasts and lymphoblastoid cells. Application to the characterization of a glycine 997 to serine substitution in alpha 1(II) collagen chains of a patient with spondyloepiphyseal dysplasia [12].
• Characterization of an arginine 789 to cysteine substitution in alpha 1 (II) collagen chains of a patient with spondyloepiphyseal dysplasia [13].
• Addition of 1,25-dihydroxyvitamin D to the diet, which is known to reduce the incidence of dyschondroplasia, resulted in an increase in c-myc production [14].
• A single base mutation in the type II procollagen gene (COL2A1) that converts glycine alpha 1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia [15].
• Interexperimental variation in the incidence of tibial dyschondroplasia of chickens that occurred in studies on the effect of dietary calcium, phosphorus and cholecalciferol metabolites was apparent from previous reports from this laboratory [16].

Biological context of Osteochondrodysplasias

• Mild spondyloepiphyseal dysplasia (Namaqualand type): genetic linkage to the type II collagen gene COL2A1 [17].
• This study confirmed the importance of dominant negative mutations of the COL2A1 gene in producing the spondyloepiphyseal dysplasia congenita phenotype [13].
• Osteopontin gene expression and alkaline phosphatase activity in avian tibial dyschondroplasia [18].
• The histopathologic characteristics of the cartilage appear to be similar in the fetus and older patient, and therefore may be useful in differentiating diastrophic dysplasia from other osteochondrodysplasias in the second trimester [19].
• Alternative splicing of exon 12 of the COL2A1 gene interrupts the triple helix of type-II collagen in the Kniest form of spondyloepiphyseal dysplasia [20].

Anatomical context of Osteochondrodysplasias

• The spondyloepiphyseal dysplasias (SEDs) and spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of skeletal dysplasias (dwarfing disorders) characterized by abnormal epiphyses, with and without varying degrees of metaphyseal irregularities, flattened vertebral bodies, and myopia [21].
• Our findings suggest that the secretory defect in pseudoachondroplasia and multiple epiphyseal dysplasia is not specific for chondrocytes, nor does it require interaction of mutant COMP with other matrix proteins prior to transport from the cell [22].
• Changes in the tibial growth plates of chickens with thiram-induced dyschondroplasia [23].
• Four experiments were conducted to study the effects of genetic strain, dietary Ca level, and feed withdrawal on growth, feed efficiency, tibia bone ash, tibial dyschondroplasia (TD), and plasma 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 25-hydroxycholecalciferol [25(OH)D3] [24].
• Reports of uncommon presentations are also described, including a controlled study on calcification of the ligamenta flava of the spine and a study involving 19 years of clinical follow-up of families with hydroxyapatite chondrocalcinosis with spondyloepiphyseal dysplasia [25].

Gene context of Osteochondrodysplasias

• COL9A3: A third locus for multiple epiphyseal dysplasia [26].
• A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity [27].
• This mutation emphasizes the importance of COL2A1 mutations in producing the spondyloepiphyseal dysplasia phenotype [12].
• Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes [28].
• The deficiency of PAPSS2 results in osteochondrodysplasias [29].

Analytical, diagnostic and therapeutic context of Osteochondrodysplasias

• OBJECTIVE: To develop transgenic mice harboring mutations in the COMP gene as animal models for pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), autosomal dominant disorders characterized by early onset osteoarthritis and epiphyseal abnormalities [30].
• Electron microscopy as an aid to diagnosis of disorders of the extracellular matrix: a new type of spondyloepiphyseal dysplasia [31].
• Eight of the group fed the imbalanced diet developed dyschondroplasia which was accompanied by a significant increase in the mean and peak GH concentrations compared with the control group but no increase in basal concentrations [32].

References