MSELENI JOINT DISEASE - A MOLECULAR-GENETIC APPROACH TO DEFINING THE ETIOLOGY

Mseleni joint disease (MJD) is an unusual form of progressive and wide spread degenerative osteoarthropathy that has been identified in sever al hundred people in the remote Mseleni region of northern Zululand. A ffected individuals experience articular discomfort in childhood and m ay be seriously handicapped as adults, often requiring prosthetic hip joint replacement. Although the condition clusters in families, there is no evidence of Mendelian inheritance and assessment of affected kin dreds has not shown any evidence of genomic imprinting, To date our mo lecular work-up has entailed the study of 47 affected individuals from MJD kindreds to investigate familial predisposition based on the inhe ritance of a subset of markers and/or genes on the human genome, parti cularly those associated with the cartilage matrix. In addition, we ha ve collected blood specimens from 111 unaffected but unrelated individ uals from the same population group in order to determine whether any relationship exists between genetic components of the human leucocyte antigen (HLA) system and the MJD phenotype. Our investigations show th e following: (i) there is no association between MJD and the HLA syste m which has previously been associated with non-Mendelian genetic cond itions; (ii) COL2A1, which has been implicated in some forms of spondy lo-epiphyseal dysplasia, may be involved in at least a subset of MJD p atients; acid (iii) type VI collagen is overabundant in degenerated hi p joint cartilage.