MAPPING OF THE GENE FOR CLEIDOCRANIAL DYSPLASIA IN THE HISTORICAL CAPE-TOWN (ARNOLD) KINDRED AND EVIDENCE FOR LOCUS HOMOGENEITY

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder, featu res of which include a patent anterior fontanelle, a bulging calvarium , hypoplasia or aplasia of the clavicles, a wide pubic symphysis, dent al anomalies, vertebral malformation, and short stature. The Cape Town kindred which is under our genetic management was originally describe d more than four decades ago and now consists of more than 1000 people . Following reports of rearrangements on chromosomes 6 and 8 in people with CCD, we have carried out linkage analyses between highly informa tion microsatellite dinucleotide repeat markers in the rearranged regi ons and the disorder in a branch of this South African CCD kindred, co nsisting of 38 subjects, 18 of whom are affected. Maximum lod scores ( at theta = 0.00) of 7.14 (for marker D6S459), 4.32 (TCTE), 4.99 (D6S45 2), 5.97 (D6S269), and 3.95 (D6S465) confirm linkage of the disorder t o the short arm of chromosome 6. Our data indicate that the CCD gene i s located within a minimal region of approximately 10 cM flanked by th e marker D6S451 distally and D6S466 proximally. This information is vi tal towards isolating and characterising the gene for CCD, and is bein g used to construct a physical map of 6p21.1-6p21.3. More importantly, mapping of the locus in the South African kindred of mixed ancestry, in which the ''founder'' of the disorder was of Chinese origin, sugges ts that a single locus is responsible for classic CCD.