Novel KIAA0825 Variants Underlie Nonsyndromic Postaxial Polydactyly

Background: Extra digits on the hands and/or feet are a frequent condition known as polydactyly. Twelve nonsyndromic polydactyly genes have been identified, including KIAA0825. Methods: Four consanguineous Pakistani families that segregate nonsyndromic postaxial polydactyly (PAP) with an autosomal recessive mode of inheritance were clinically and genetically evaluated. Exome sequencing or genotyping of polymorphic microsatellite markers followed by Sanger sequencing were used to identify the variants underlying the PAP etiology. Results: Three novel KIAA0825 variants were identified that segregate with PAP: a nonsense variant c.2319G>A; p.(Trp773*) in two families; a missense variant c.970G>T; p.(Val324Phe) in one family; and a four amino acids in-frame deletion c.2743_2754del; p.(Gln915_Val918del) in one family. The nonsense variant segregated in families with PAP type B (PAPB), while the missense and the in-frame deletion variants segregated with PAP type A and B. Conclusions: The findings of this study expanded the clinical and genetic spectrum of PAP due to KIAA0825 variants including the first KIAA0825 variant specific to PAPB.