Discovery
Multiple epiphyseal dysplasia was described separately by Ribbing and Fairbank in the 1930s.
In 1994, Ralph Oehlmann's group mapped MED to the peri-centromeric region of chromosome 19, using genetic linkage analysis. Michael Briggs' group mapped PSACH to the same area. COMP gene was fistly linked to MED and PSACH in 1995. Later on, in 1995, the group led by Knowlton did a "high-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12". Research on COMP led to mouse models of the pathology of MED. In 2002, Svensson's group generated a COMP-null mouse to study the COMP protein in vivo. However, these mice showed no anatomical, histological, or even ultrastructural abnormalities and none of the clinical signs of PSACH or MED. Lack of COMP was not compensated for by any other protein in the thrombospondin family. This study confirmed that the disease is not caused by reduced expression of COMP. In 2007, Piròg-Garcia's group generated another mouse model carrying a mutation previously found in a human patient. With this new model, they were able to demonstrate that reduced cell proliferation and increased apoptosis are significant pathological mechanisms involved in MED and PSACH. In 2010, this mouse model allowed a new insight into myopathy and tendinopathy, which are often associated with PSACH and MED. These patients show increased skeletal muscle stress, as indicated by the increase in myofibers with central nuclei). Myopathy in the mutant mouse results from underlying tendinopathy, because the transmission of forces is altered from the normal state. There is a higher proportion of larger diameter fibrils of collagen but the cross-sectional area of whole mutant tendons was also significantly less than that of the wild-type tendons causing joint laxity and stiffness, easy tiringness and weakness. This study is important because those diseases are often mistaken for neurological problems, since the doctor can detect a muscle weakness. This include a lot of painful and useless clinical neurological examination prior to the correct diagnosis. In this work, the researchers suggest to the pediatric doctor to perform x-rays before starting the neurological assessment, to exclude the dysplasia.
COL91A mutation was discovered in 2001.
Read more about this topic: Multiple Epiphyseal Dysplasia
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