A Novel Variant in the Cyto-Tail of Gene Underlying Isolated Postaxial Polydactyly.

BACKGROUND

Polydactyly is one of the most common hereditary limb malformations, characterized by presence of additional digits in hands and/or feet. It is present either in isolated form or in combination with other features. Preaxial polydactyly with extra digit on the outside of the thumb or big toe, and postaxial polydactyly with extra digit on the outside of the little finger or little toe are the two main forms of polydactyly.

METHODS AND RESULTS

In the present study, two unrelated consanguineous families segregating PAP in an autosomal recessive manner were investigated. Whole exome sequencing, followed by segregation analysis using Sanger sequencing, revealed a homozygous missense variant [c.1792 G>A; p.(Gly598Arg); NM_005631.5] in the in both families Proteins SMO, PTCH, and GLI act as major components of the Sonic hedgehog pathway, which transmits signals to embryonic cells for cellular differentiation. Homology modeling revealed that the variant in SMO may disrupt proper protein folding and interaction with other molecules.

CONCLUSION

Our study has revealed the second direct involvement of a sequence variant in the causing isolated polydactyly. This study will highlight the importance of the inclusion of the gene in screening individuals presenting polydactyly in hands and feet.