Abstract

Background: Polydactyly or hexadactyly is a familiar limb defect that either occurs as an isolated entity (non-syndromic) or is associated with severe (syndromic) morphological phenotypes. Generally, it appears due to a defect in the anteroposterior patterning during limb development.
Methods: Here, we present a proband having non-syndromic post-axial polydactyly (PAP) evaluated using whole exome sequencing followed by Sanger sequencing. Furthermore, 3D protein modeling was executed for the normal and mutated IQ domain-containing protein E (IQCE) gene.
Results: WES analysis revealed an already reported bi-allelic variant (c.395-1 G>A) in the IQCE gene, previously associated with PAP 7. Furthermore, 3D modeling revealed significant fluctuations in the IQCE protein secondary structure, thus affecting downstream signaling.
Conclusion: The work presented validated the significant role of the IQCE gene in the development and patterning of human limbs.

Key words: PAPA, IQCE, reported variant, Pakistani population, 3D modeling, WES.