Abstract
Multiple epiphyseal dysplasia (MED) is a mild chondrodysplasia affecting the structural integrity of cartilage and causing early-onset osteoarthrosis in adulthood. The condition is genetically heterogeneous. Mutations in the COMP gene and in two genes (COL9A2; COL9A3), coding respectively for the α2(IX) and α3(IX) chains of type IX collagen, can cause the autosomal dominant forms of MED. Mutations in the DTDST gene have recently been identified in a recessive form of MED. However, for the majority of MED cases, the genetic defect still remains undetermined. We report a three-generation family with an autosomal dominant form of MED, characterised by normal stature, joint pain in childhood and early-onset osteoarthrosis, affecting mainly the hips and knees. Based on discordant inheritance among affected individuals linkage of the phenotype to the COMP, COL9A1, COL9A2, COL9A3 genes was excluded. Our study provides evidence that at least another locus, distinct from COL9A1, is involved in autosomal dominant MED.
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Acknowledgements
We thank the family for their very fruitful cooperation. The Flanders Fund for Scientific Research (Grant G.0013.97 to GR Mortier) and the Arthritis Research Campaign (Grant B0644 to MD Briggs) funded this work. MD Briggs is an ARC Research Fellow. Genotyping was performed in the ARC Epidemiology Unit, within the School of Epidemiology and Health Science, University of Manchester.
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Mortier, G., Chapman, K., Leroy, J. et al. Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes. Eur J Hum Genet 9, 606–612 (2001). https://doi.org/10.1038/sj.ejhg.5200690
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DOI: https://doi.org/10.1038/sj.ejhg.5200690
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