Genetic mapping of cleidocranial dysplasia and evidence of a microdeletion in one family.

Cleidocranial dysplasia (CCD) is an autosomal, dominantly inherited disorder of high penetrance affecting skeletal ossification and tooth development. Typically, affected individuals have hypoplastic/aplastic clavicles, patent fontanelles and sutures, supernumerary teeth, and short stature. We have used a candidate locus approach to map the responsible gene in two families with typical features of CCD. Linkage was established between CCD and four loci (D6S426, D6S451, D6S459, TCTE1) that span a region of 10 cM on chromosome 6p. A maximum lod score, Zmax, of 4.1 at a recombination fraction of zero was obtained at D6S451. One highly polymorphic microsatellite from this region (D6S459) showed allelic loss in all affected members of one family with two different sets of primers. The presence of a deletion in this area was confirmed by Southern blot analysis using a probe derived from the amplification product of the D6S459 marker. The data assign a gene for CCD to chromosome 6p21 and suggest that a microdeletion within an area of tight linkage to the CCD-phenotype has been identified.