By systematically reviewing the gene-phenotype relationship, we found that GLI3p.P394fs18x mutation might be specific for isolated postaxial polydactyly.
To the best of our knowledge, the present study reports on the first familial case of nonsyndromic postaxial polydactyly due to the GLI3 variant in Pakistani population.
The present study reports two cases: first, a familial case of Greig Cephalopolysyndactyly Syndrome (GCPS); the second is a sporadic case with both postaxial polydactyly (PAP) type A and B. Resequencing of GLI3 gene reveals a previously reported nonsense truncation mutation g.42007251G > A (p.R792X; rs121917714) in the GCPS family and a novel single nucleotide insertion g.42004239_42004240insA (p.E1478X) in the sporadic case of postaxial polydactyly (PAP).
Two types of PAP including PAP-A, representing the development of well-formed extra digit, and PAP-B, representing the presence of rudimentary fifth digit, have been described.
Human GLI3 gene mutations have been identified in several phenotypes of digital abnormality such as Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type-IV (PPD-IV) and postaxial polydactyly.
A rudimentary extra fifth digit characterises type B. Mutations in the GLI3 gene are associated with postaxial polydactyly in some families and a second locus has been identified on chromosome 13 but the majority of cases remain unexplained.