A Frameshift Variant in KIAA0825 Causes Postaxial Polydactyly

Postaxial polydactyly (PAP) is characterized by counterproductive 5th digit (pinky finger) duplication on hands and/or feet which often leads to functional complications. To date, at least 11 genes involved in causing various types of nonsyndromic polydactylies have been reported. In the present study, a consanguineous family of Sindhi origin with a segregating nonsyndromic form of PAP in an autosomal recessive manner was clinically and genetically evaluated. Genotyping, using polymorphic microsatellite markers, established linkage in the family on chromosome 5q15 harboring the KIAA0825 gene (MIM 617266). Sequence analysis of the gene revealed a novel frameshift variant leading to a premature stop codon [c.143delG, p.(Cys48Serfs*28)]. This is only the 4th novel variant in the KIAA0825 gene that leads to PAP type A10 (PAPA10) (MIM 618498). Identification of variants in the PAP causative gene will support the diagnosis of patients with limb malformations in the Pakistani population.

Automated summary

The study clinically and genetically evaluated a consanguineous family of Sindhi origin with a segregating nonsyndromic form of postaxial polydactyly (PAP) in an autosomal recessive manner. Linkage was established on chromosome 5q15 harboring the KIAA0825 gene, and a novel frameshift variant was identified, which is the 4th novel variant causing PAP type A10. Identification of variants in the PAP causative gene may aid in the diagnosis of limb malformations in the Pakistani population.