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

• Published in: Nature (London) Vol. 352; no. 6335; pp. 539 - 540
• Main Authors: Vortkamp, Andrea, Gessler, Manfred, Grzeschik, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 08-08-1991; Nature Publishing Group
• Subjects: Biological and medical sciences; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 7; Complex syndromes; DNA-Binding Proteins - genetics; Facial Bones - abnormalities; Female; Genetic Linkage; Genetics; Humans; Hybrid Cells - cytology; In Vitro Techniques; Kruppel-Like Transcription Factors; Male; Medical disorders; Medical genetics; Medical research; Medical sciences; Nerve Tissue Proteins; Receptor, Epidermal Growth Factor - genetics; Repressor Proteins; Restriction Mapping; Skull - abnormalities; Syndactyly - genetics; Syndrome; Transcription Factors; Translocation; Translocation, Genetic; Xenopus Proteins; Zinc Finger Protein Gli3; Zinc Fingers - genetics; Chromosomal aberration; Genetic mapping; Human; Nervous system diseases; Stomatology; Family study; Diseases of the osteoarticular system; Dysmorphic facies; Hand; Foot; Malformation; Syndactyly; Abnormal chromosome; Mutation; Complex syndrome; Abnormal C7 chromosome; GREIG syndrome; Physical map; Macrocephaly; Chromosome translocation
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/352539a0

The Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans. 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 7p13 by three balanced translocations associated with GCPS in different families. This assignment is corroborated by the detection of two sporadic GCPS cases carrying overlapping deletions in 7p13 (ref. 7), as well as by tight linkage of GCPS to the epidermal growth factor receptor gene in 7p12-13 (ref. 8). Of the genes that map to this region, those encoding T cell receptor-gamma, interferon-beta 2, epidermal growth factor receptor, and Hox1.4, a potential candidate gene for GCPS, have been excluded from the region in which the deletions overlap. Here we show that two of the three translocations interup the GLI3 gene, a zinc-finger gene of the GLI-Krüppel family already localized to 7p13 (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.