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GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families

Naturevolume 352pages539540 (1991) | Download Citation



THE Greig cephalopolysyndactyly syndrome (GCPS) is an auto-somal dominant disorder affecting limb and craniofacial development in humans1,2. GCPS-affected individuals are characterized by postaxial polysyndactyly of hands, preaxial polysyndactyly of feet, macroephaly, a broad base of the nose with mild hypertelorism and a prominent forehead. The genetic locus has been pinpointed to chromosome 7pl3 by three balanced translocations associated with GCPS in different families3,4,19. This assignment is corroborated by the detection of two sporadic GCPS cases carrying overlapping deletions in 7pl3 (ref. 7), as well as by tight linkage of GCPS to the epidermal growth factor receptor gene in 7pl2–13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-γ, interferon-β2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap7,9. Here we show that two of the three translocations interrup the GLI3 gene, a zinc-finger gene of the GLI-Krüppel family already localized to 7pl3 (refs 5, 6). The breakpoints are within the first third of the coding sequence. In the third translocation, chromosome 7 is broken at about 10 kilobases downstream of the 3' end of GLI3. Our results indicate that mutations disturbing normal GLI3 expression may have a causative role in GCPS.

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  1. Institut für Humangenetik, Philipps-Universität, Bahnhofstrasse 7a, D-3550, Marburg, Germany

    • Andrea Vortkamp
    • , Manfred Gessler
    •  & Karl-Heinz Grzeschik


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