GENETIC-HETEROGENEITY AMONG CRANIOSYNOSTOSIS SYNDROMES - MAPPING THE SAETHRE-CHOTZEN SYNDROME LOCUS BETWEEN D7S513 AND D7S516 AND EXCLUSIONOF JACKSON-WEISS AND CROUZON SYNDROME LOCI FROM 7P

Saethre-Chotzen, Crouzon, and Jackson-Weiss syndromes are craniosynost otic autosomal dominant conditions with a wide variability in expressi on. Saethre-Chotzen has been mapped to chromosome 7p by L. A. Brueton et al. (1992, J. Med. Genet. 29: 681-685), the Greig cephalopolysyndac tyly gene was identified at 7p13 by A. Vortkamp et al. (1991, Nature 3 52: 539-540), and many cases of craniosynostosis have been associated with 7p deletions. We confirmed linkage of the Saethre-Chotzen syndrom e locus to chromosome 7p. The tightest linkage was to locus D7S493 (Z = 5.04, theta = 0.00), and linkage and haplotype analyses refined the location of the gene to the region between D7S513 and D7S516. Jackson- Weiss and Crouzon syndrome loci were analyzed using markers spanning t he entire 7p arm and were excluded, proving that they are nonallelic t o Saethre-Chotzen, Greig cephalopolysyndactyly, and the del(7p) syndro mes. (C) 1994 Academic Press, Inc.