Saethre-Chotzen, Crouzon, and Jackson-Weiss syndromes are craniosynostotic autosomal dominant conditions with a wide variability in expression. Saethre-Chotzen has been mapped to chromosome 7p by L. A. Brueton et al. (1992, J. Med. Genet. 29: 681-685), the Greig cephalopolysyndactyly gene was identified at 7p13 by A. Vortkamp et al. (1991, Nature 352: 539-540), and many cases of craniosynostosis have been associated with 7p deletions. We confirmed linkage of the Saethre-Chotzen syndrome locus to chromosome 7p. The tightest linkage was to locus D7S493 (Z = 5.04, θ = 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 the entire 7p arm and were excluded, proving that they are nonallelic to Saethre-Chotzen, Greig cephalopolysyndactyly, and the del(7p) syndromes.

We examined the effects of partially purified ovine GRF on medium growth hormone and tissue cyclic AMP and cyclic GMP content of incubated pituitary explants. Although hypothalamic extracts that contained numerous releasing factors had increased both cyclic AMP and cyclic GMP, the purified GRF promoted the accumulation of cyclic GMP, but not cyclic AMP. Six μg of the GRF increased medium growth hormone 240% above flasks containing only control buffer. These data support the concept that cyclic GMP is an important intracellular mediator of growth hormone release.