LINKAGE ANALYSIS OF MESOMELIC DYSPLASIA, KANTAPUTRA TYPE
Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal dominant skeletal dysplasia characterized by bilateral symmetrical marked shortening of the ulnae and shortening and bowing of the radii. The proximal fibula is usually short and synostoses are present between the tibia and fibula and the small malformed calcaneus and talus. The prominent calcanei on the ventral surfaces of the distal fibulae are a characteristic feature of this new syndrome. Carpal and tarsal synostoses are present in some affected people. We studied this Thai family in which 15 members in 3 generations were affected. With reference to the breakpoints of a balanced translocation [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a skeletal dysplasia that appears similar to MDK, a linkage analysis was performed using 50 CA-repeat markers mapped to nearby regions (2q22-q34 and 8p24-p21) of the translocation breakpoints. The results clearly ruled out a linkage of MDK to marker loci at the 8p24-p21 region, whereas all nine affected members available for the study shared a haplotype at four loci (D2S2284, D2S326, D2S2188, and D2S2314) spanning about 22.7cM in the 2q24-q32 region. The computer-assisted two-point linkage analysis revealed maximum logarithm of odds (lod) scores of 4.82, 4.21, 4.82, and 4.21 (θ = 0) at these loci, respectively. These data indicated that the MDK locus is in the vicinity of D2S2284 and D2S2188 loci that are the most likely mapped to 2q24-q32.
