Journal of Scientific Research Vol. 61, 2017 : 121-129 Banaras Hindu University, Varanasi ISSN : 0447-9483 GLI3 MEDIATED POLYDACTYLY : A REVIEW Rashmi Patel 1 , Chandra Bhan Singh 1 , Subodh Kumar Singh 2 , Akhtar Ali 1 * 1 Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi-221005, India 2 GS Memorial Plastic Surgery Hospital & Trauma Center, Varanasi, India *Corresponding author : Email : akhtar_genetics@yahoo.co.in; akhtar@bhu.ac.in Cell No. : +918960236620 Abstract GLI3 is one of the major pathogenic genes associated with both syndromic and non-syndromic polydactyly. Mutations in different domains of GLI3 exhibit variable type of clinical manifestations viz. Greig Cephalopolysyndactyly Syndrome (GCPS), Pallister-Hall Syndrome, Acrocallosal Syndrome, Pre-axial Polydactyly type IV, Post- axial Polydactyly type A, trigonocephaly with craniosynostosis and polydactyly and some types of oral–facial-digital syndrome. The present review demonstrates the clinical features of syndromic and non-syndromic polydactyly and recent progresses in underlying molecular genetics of GLI3. This review further demonstrates phenotypes with overlapping manifestations, genetic heterogeneity, and distinct phenotypes generated from mutations in GLI3. These updates improve our understanding of the GLI3 mediated polydactyly and have implications on genetic counselling. Keywords : Polydactyly, GLI3, GCPS, PHS, Mutation, Limb 3 Polydactyly refers to the presence of more than the usual number of fingers or toes (figure 1). Its incidence is 1:1,000 live births (Bellovits 2003, Phelps 1985) however frequency differs among racial groups (Stevenson et al. 1966). Often the extra digit is incompletely formed and lacks normal muscular development. Polydactyly can be classified into preaxial, central, and postaxial types depending on the location of the duplication. About 79 % of all duplications are postaxial, 15 % are preaxial and remaining 6 % are central (Phelps et al. 1985). If the hand is affected, the extra digit is most commonly medial or lateral rather than central. In the foot, the extra toe is usually on the lateral side. Polydactyly can occur as an isolated malformation or as part of a genetic syndrome (Mumoli et al. 2008). Currently, there are about 221 syndromes described with polydactyly and 120 syndromes with oligodactyly (Phadke and Sankar 2010). Despite this wide prevalence of limb abnormalities, to date only, 84 genes have been associated with syndromes that include limb defects, 15 of which have described polydactyly (Phadke and Sankar 2010). GLI3 is one of the major pathogenic genes, expressed early in development and is a downstream mediator of the sonic hedgehog pathway associated with both syndromic and non-syndromic polydactyly. GLI3 is a large gene located on chromosome locus 7p14.1 with exons spanning 296 kb. The current reference sequence for the cDNA is an 8,228 nucleotide sequence: NM_000168.5.