LINKAGE OF PFEIFFER-SYNDROME TO CHROMOSOME-8 CENTROMERE AND EVIDENCE FOR GENETIC-HETEROGENEITY

Pfeiffer syndrome (PS) is an autosomal dominant disorder characterized by craniosynostosis, midfacial hypoplasia, and broad thumbs and great toes. We examined 129 individuals from 11 families with PS and perfor med linkage studies using microsatellite markers spanning the entire g enome. Strongest support for linkage was with DNA markers (D8S255, GAT A8G08) from chromosome 8. Obligate crossovers exclude close linkage to this region in six families, and there was significant evidence for g enetic heterogeneity. A multipoint lod score of 7.15 was obtained in f ive families. The 11 cM interval between D8S278 and D8S285 contains on e gene for PS and also spans the centromere of chromosome 8.