Abstract
The human phenotypes caused by mutations in GLI3 are a prototype for the utility of clinical analysis to unravel gene function. When the human studies were coupled with basic research, the pathway to understanding gene function was easier to discern and more rapidly accomplished. Outlining the series of discoveries that led to our current understanding of GLI 3 and genotype-phenotype correlation is useful to demonstrate how these discoveries can be facilitated in the future.
Keywords
- Imperforate Anus
- Hypothalamic Hamartoma
- Postaxial Polydactyly
- Preaxial Polydactyly
- Acrocallosal Syndrome
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The surname is pronounced “greg”, with a trilled r. The surname of the composer Edward Grieg is pronounced “greeg”.
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References
Greig DM. Oxycephaly. Edinb Med J 1926; 33:189–218.
Temtamy SA, McKusick VA. The genetics of hand malformations. Birth Defects Orig Artic Ser 1978; 14(i–xviii):1–619.
Greig DM. Hypertelorism. Edinb Med J 1924; 31:560–593.
Gorlin RJ, Cohen Jr MM, Hennekam RCM. Greig cephalopolysyndactyly syndrome. Syndromes of the Head and Neck. 4th ed. New York: Oxford University Press, 2001:995–996.
Biesecker LG. GLI3 and the Pallister-Hall and Greig cephalopolysyndactyly syndromes. In: Epstein CJ, Erickson RP, Wynshaw-Boris A, eds. Inborn errors of development: The molecular basis of clinical disorders of morphogenesis. Oxford: Oxford University Press, 2004:257–264.
Motegi T, Ohuchi M, Ohtaki C et al. A craniosynostosis in a boy with a del(7)(p15.3p21.3): Assignment by deletion mapping of the critical segment for craniosynostosis to the mid-portion of 7p21. Hum Genet 1985; 71:160–162.
Tommerup N, Nielsen F. A familial reciprocal translocation t(3;7) (p21.1;p13) associated with the Greig polysyndactyly-craniofacial anomalies syndrome. Am J Med Genet 1983; 16:313–321.
Bacchichetti C, Artifoni L, Zanardo V. Deletions of the short arm of chromosome 7 without craniosynostosis. Clin Genet 1982; 21:348–349.
Vortkamp A, Gessler M, Grzeschik K-H. GLI3 zinc finger gene interrupted by translocations in Greig syndrome families. Nature 1991; 352:539–540.
Hall JG, Pallister SK, Clarren SK et al. Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, and postaxial polydactyly-A new syndrome? Part I: Clinical, causal, and pathogenetic considerations. Am J Med Genet 1980; 7:47–74.
Sills IN, Rapaport R, Robinson P et al. Familial Pallister-Hall syndrome: Case report and hormonal evaluation. Am J Med Genet 1993; 47:321–325.
Topf KF, Kletter GB, Kelch RP et al. Autosomal dominant transmission of the Pallister-Hall syndrome. J. Pediatr 1993; 123:943–946.
Biesecker LG, Topf K, Graham Jr JM. Familial Pallister-Hall syndrome. J Med Genet 1994; 31:740.
Penman Splitt M, Wright C, Perry R et al. Autosomal dominant transmission of the Pallister-Hall syndrome. Clin Dysmorphol 1994; 3:301–308.
Sama A, Mason JD, Gibbin KP et al. Familial Pallister-Hall syndrome. J Med Genet 1994; 31:740.
Thomas HM, Todd PJ, Heaf D et al. Recurrence of Pallister-Hall syndrome in two sibs. J Med Genet 1994; 31:145–147.
Biesecker LG, Abbott M, Allen J et al. Report from the workshop on Pallister-Hall syndrome and related disorders. Am J Med Genet 1996; 65:76–81.
Kang S, Allen J, Graham Jr JM et al. Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome. J Med Genet 1997; 34:441–446.
Kang S, Graham Jr JM, Olney AH et al. GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome. Nature Genet 1997; 15:266–268.
Baraitser M, Winter RM, Brett EM. Greig cephalopolysyndactyly: Report of 13 affected individuals in three families. Clin Genet 1983; 24:257–265.
Brueton L, Huson SM, Winter RM et al. Chromosomal localisation of a developmental gene in man: direct DNA analysis demonstrates that Greig cephalopolysyndactyly maps to 7p13. Am J Med Genet 1988; 31:799–804.
Vortkamp A, Franz T, Gessler M et al. Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt). Mamm Genome 1992; 3:461–463.
Bose J, Grotewold L, Ruther U. Pallister-Hall syndrome phenotype in mice mutant for Gli3. Hum Mol Genet 2002; 11:1129–1135.
Aza-Blanc P, Kornberg T. Ci: A complex transducer of the Hedgehog signal. Trends Genet 1999; 15:458–462.
Aza-Blanc P, Ramírez-Weber F-A, Laget M-P et al. Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell 1997; 89:1043–1053.
Biescker LG. Strike three for GLI3. Nature Genet 1997; 17:259–260.
Kalff-Suske M, Wild A, Topp J et al. Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome. Hum Mol Genet 1999; 8:1769–1777.
Sobetzko D, Eich G, Kalff-Suske M et al. Boy with syndactylies, macrocephaly, and severe skeletal dysplasia: Not a new syndrome, but two dominant mutations (GLI3 E543X and COL2A1 G973R) in the same individual. Am J Med Genet 2000; 90:239–242.
Kalff-Suske M. Gene symbol: GLI3. Disease: Greig cephalopolysyndactyly syndrome. Hum Genet 2000; 107:203.
Kalff-Suske M. Gene symbol: GLI3. Disease: Pallister-Hall syndrome. Hum Genet 2000; 107:204.
Kalff-Suske M, Paparidis Z, Bornholdt D et al. Gene symbol: GLI3. Disease: Pallister-Hall syndrome. Hum Genet 2004; 114:403.
Killoran CE, Abbott M, McKusick VA et al. Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: Clinical and molecular analysis. Clin Genet 2000; 58:28–30.
Kroisel PM, Petek E, Wagner K. Phenotype of five patients with Greig syndrome and microdeletion of 7p13. Am J Med Genet 2001; 102:243–249.
Wild A, Kalff-Suske M, Vortkamp A et al. Point mutations in human GLI3 cause Greig syndrome. Hum Mol Genet 1997; 6:1979–1984.
Williams PG, Hersh JH, Yen FF et al. Greig cephalopolysyndactyly syndrome: Altered phenotype of a microdeletion syndrome due to the presence of a cytogenetic abnormality. Clin Genet 1997; 52:436–441.
Turner C, Killoran C, Thomas NS et al. Human genetic disease caused by de novo mitochondrial-nuclear DNA transfer. Hum Genet 2003; 112:303–309.
Radhakrishna U, Bornholdt D, Scott HS et al. The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; No phenotype prediction from the position of GLI3 mutations. Am J Hum Genet 1999; 65:645–655.
Wagner K, Kroisel PM, Rosenkranz W. Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: Hemizygosity for PGAM2 and TCRG genes. Genomics 1990; 8:487–491.
Pelz L, Kruger G, Gotz J. The Greig cephalopolysyndactyly syndrome. Helv Paediatr Acta 1986; 41:381–382.
Pettigrew AL, Greenberg F, Caskey CT et al. Greig syndrome associated with an interstitial deletion of 7p: Confirmation of the localization of Greig syndrome to 7p13. Hum Genet 1991; 87:452–456.
Driess S, Freese K, Bornholdt D et al. Gene symbol: GLI3. Disease: Greig cephalopolysyndactyly syndrome. Hum Genet 2003; 112:103.
Freese K, Driess S, Bornholdt D et al. Gene symbol: GLI3. Disease: Pallister-Hall syndrome. Hum Genet 2003; 112:103.
Friez MJ, Stevenson RE. Pallister-Hall syndrome. Proc Greenwood Genet Cen 2000; 19:51–55.
Galasso C, Scire G, Fabbri F et al. Long-term treatment with growth hormone improves final height in a patient with Pallister-Hall syndrome. Am J Med Genet 2001; 99:128–131.
Johnston JJ, Olivos-Glander I, Turner J et al. Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet 2003; 123A:236–242.
Ng D, Johnston JJ, Turner JT et al. Gonadal mosaicism in severe Pallister-Hall syndrome. Am J Med Genet 2004; 124A:296–302.
Bianchi DW, Cirillo-Silengo M, Luzzatti L et al. Interstitial deletion of the short arm of chromosome 7 without craniosynostosis. Clin Genet 1981; 19:456–461.
Marks K, Hill L, Chitham RG et al. Interstitial deletion of chromosome 7p detected antenatally. J Med Genet 1985; 22:316–318.
Debeer P, Peeters H, Driess S et al. Variable phenotype in Greig cephalopolysyndactyly syndrome: Clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations. Am J Med Genet 2003; 120A:49–58.
Kremer S, Minotti L, Thiriaux A et al. Epilepsy and hypothalamic hamartoma: Look at the hand Pallister-Hall syndrome. Epileptic Disord 2003; 5:27–30.
Bai CB, Stephen D, Joyner AL. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev Cell 2004; 6:103–115.
Li Y, Zhang H, Choi SC et al. Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis. Dev Biol 2004; 270:214–231.
Persson M, Stamataki D, te Welscher P et al. Dorsal-ventral patterning of the spinal cord requires Gli3 transcriptional repressor activity. Genes Dev 2002; 16:2865–2878.
Shin S, Kogerman P, Lindström E et al. GLI3 mutations in human disorders mimic Drosophila Cubitus interruptus protein functions and localization. Proc Natl Acad Sci USA 1999; 96:2880–2884.
Wang B, Fallon J, Beachy P. Hedgehog-regulated processing of Gli3 produces an anterior/poterior repressor gradient in the developing vertebrate limb. Cell 2000; 100:423–434.
Ruiz i Altaba A. Gli proteins encode context-dependent positive and negative functions: Implications for development and disease. Development 1999; 126:3205–3216.
Asch AJ, Myers GJ. Benign familial macrocephaly: Report of a family and review of the literature. Pediatrics 1976; 57:535–539.
Radhakrishna U, Wild A, Grzeschik K-H et al. Mutation in GLI3 in post-axial polydactyly type A. Nature Genet 1997; 17:269–270.
Elson E, Perveen R, Donnai D et al. De novo GLI3 mutation in acrocallosal syndrome: Broadening the phenotypic spectrum of GLI3 defects and overlap with murine models. J Med Genet 2002; 39:804–806.
Gorlin RJ, Cohen Jr MM, Hennekam RCM. The oral facial digital syndromes. In: Gorlin RJ, Cohen Jr MM, Hennekam RCM, eds. Syndromes of the head and neck. 4th ed. Oxford: Oxford University Press, 2001.
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Biesecker, L.G. (2006). Human Correlates of GLI3 Function. In: Hedgehog-Gli Signaling in Human Disease. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-33777-6_10
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DOI: https://doi.org/10.1007/0-387-33777-6_10
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