Genetic mapping of a locus for multiple epiphyseal dysplasia (EDM 2) to a region of chromosome 1 containing a type IX collagen gene

Clinical phenotype and molecular diagnosis of multiple epiphyseal dysplasia with relative hip sparing during childhood (EDM2)

“…The pattern of joint involvement together with normal stature, recurrent development of free articular bodies leading to joint blocking, abnormalities in the leg axis and the obviously autosomal dominant mode of inheritance, fits best into the subtypes linked to collagen type IX genes. The clinical phenotype in our family closely resembles the one described for the mutations in COL9A2 and in COL9A3 in several families [Briggs et al, 1994;Muragaki et al, 1996a;van Mourik et al, 1998;Holden et al, 1999]. In addition to these reports, adult patients from our family had a high incidence of free articular bodies.…”

“…In some patients short stature and brachydactyly are present, indicating that the severity of the phenotype linked to the EDM1-locus may vary considerably. Briggs et al [1994] mapped a second locus to chromosome 1 into the region of COL9A2 and subsequently mutations in this gene have been identified in several MED patients (EDM2). Typically, affected individuals have less or even no obvious hip involvement during childhood.…”

Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels

“…Linkage studies in the EDM families demonstrated three loci for the disease, one of which was at or near the chromosome 1 locus for COL9A2 (Briggs et al, 1994). Subsequently, an RNA splicing mutation that caused exon skipping and an in-frame loss of 12 codons was found in one kindred (Muragaki et al, 1996).…”

Skeletal dysplasias detectable by DNA analysis

“…Indeed the Insley-Astley syndrome (Insley and Astley, 1974) specifically identifies patients with deafness, spondyloepiphyseal dysplasia and osteoarthritis with likely autosomal recessive inheritance in whom ophthalmic features were conspicuously absent. As no other COLllA2 mutations have been reported in unrelated pedigrees to date, it is not uossible to consider the range of A possible role for collagen type M in skeletal disorders was first suspected following the mapping of a large family with autosomal dominant multiple epiphyseal dysplasia (MED) to chromosome 1, near the COL9A2 locus (Briggs et al, 1994). Subsequently a Dutch family with MED has been reported with a disease causing mutation in the COL9A2 gene (Muragaki et al, 1996a).…”