Familial calcium crystal diseases: what have we learned?

The spectrum of heterotopic calcification or ossification is expanding beca use of the reports of several kindreds with calcium pyrophosphate depositio n disease, apatite deposition disease, and others with less common syndrome s associated with extracellular matrix calcification, such as fibrodysplasi a ossificans progressiva and related syndromes. Genomic DNA studies in both humans and mice provide a shortcut to understanding the genetic basis of p romotion and prevention of ECM calcification. Mutation in the COL2A1 gene h as been identified in one family with spondyloepiphyseal dysplasia and calc ium pyrophosphate and apatite crystalline deposits. In another kindred with precocious osteoarthritis without spondyloepiphyseal dysplasia, the phenot ype was linked to markers of chromosome 8. In four other kindreds, the phen otypes were linked to an area of chromosome 5p. Two genes located in this r egion, which are expressed in articular cartilage, are being investigated a s possible calcium pyrophosphate deposition disease genes. The results of l inkage studies in three kindreds with articular/periarticular ADD with the COL2A1 gene were noninformative. Two different mouse mutations, the ank/ank and the ttw/ttw mice, are associated with intra-articular and ligament apa tite deposits caused by a decrease in extracellular pyrophosphate concentra tions, mimicking human arthritis caused by apatite deposition disease. Muta tions in the matrix GLA protein, both in mice and in humans, are also assoc iated with vascular and articular calcification. These mouse mutations prov ide cutting-edge information in the investigation of the mechanisms of apat ite deposition in humans, (C) 2001 Lippincott Williams & Wilkins, Inc.