GENETIC-LINKAGE OF THE TRICHODENTOOSSEOUS SYNDROME TO CHROMOSOME 17Q21

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by var iable clinical expression, The principal clinical features include kin ky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones, Possible genetic lin kage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown, We have identified four multiplex famili es (n = 63, 39 affected, 24 unaffected) from North Carolina segregatin g TDO, We previously have excluded a major locus for TDO in the ABO re gion for these families, Utilizing a genome-wide search strategy, we o btained conclusive evidence for linkage of the TDO syndrome locus to m arkers on chromosome 17q21 (D17S791, Z(max) = 10.54, Theta = 0.00) wit h no indication of genetic heterogeneity, Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17 S932 and D17S941, This finding represents the first step towards isola tion and cloning of the TDO gene, Identification of this gene has impo rtant implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.