GLI3 ZINC-FINGER GENE INTERRUPTED BY TRANSLOCATIONS IN GREIG SYNDROME FAMILIES

被引:467
作者
VORTKAMP, A
GESSLER, M
GRZESCHIK, KH
机构
[1] Institut für Humangenetik, Philipps-Universität, D-3550 Marburg
关键词
D O I
10.1038/352539a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
THE Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder affecting limb and craniofacial development in humans 1,2. 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 7p13 by three balanced translocations associated with GCPS in different families 3,4,19. 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 7,9. Here we show that two of the three translocations interrupt the GLI3 gene, a zinc-finger gene of the GLI-Kruppel 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.
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页码:539 / 540
页数:2
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