GENETIC-MAPPING OF THE CLEIDOCRANIAL DYSPLASIA (CCD) LOCUS ON CHROMOSOME BAND 6P21 TO INCLUDE A MICRODELETION

Cleidocranial dysplasia (CCD) is a generalized skeletal dysplasia with autosomal dominant inheritance. Recently, the CCD disease locus was l ocalized to 23 Mundlos et al., 1995 and 17 cM regions Feldman et al ., 1995, of chromosome band 6p21 by linkage studies of seven afflicte d families. Of note, the 23 cM region contained a microdeletion detect ed in one family at D6S459, an interval that was excluded in the 17 cM overlapping region. Here, linkage of CCD to 6p21 was independently co nfirmed with a maximal two-point LOD score of Z=5.12 with marker D6S45 2 at theta=0.00. Recombinant events in two affected individuals define d a CCD region of 7 cM from D6S465 to D6S282, which overlapped with th e CCD region containing the microdeletion but did not overlap with the 17 cM critical region from D6S282 to D6S291. These results suggest th e refined localization of the CCD region to 6 cM spanning markers D6S4 38 to D6S282, thereby reviving the possibility that the CCD gene lies within the microdeletion at D6S459.