All of these missense mutations and the polymorphism are found in the single A-domain of matrilin-3, which is encoded by exon 2 of MATN3. Interestingly, a form of hand osteoarthritis (MIM# 607850) has been linked to a p.Thr303Met mutation located in the first EGF repeat of matrilin-3 [Stefansson et al., 2003], while a recessive form of spondyloepimetaphyseal dysplasia (MIM# 608728) results from homozygosity for a mutation (p.Cys304Ser) at the neighboring residue [Borochowitz et al., 2004]. Here, MATN3 is linked to spondyloepimetaphyseal dysplasia.