A Frameshift Variant in KIAA0825 Causes Postaxial Polydactyly

Area of Science:

• Genetics
• Medical Genetics
• Human Genetics

Background:

• Postaxial polydactyly (PAP) is a common congenital limb malformation characterized by duplication of the fifth digit.
• It can lead to functional complications and has a complex genetic etiology with multiple causative genes identified.
• Nonsyndromic PAP, inherited in an autosomal recessive manner, suggests specific genetic underpinnings.

Purpose of the Study:

• To clinically and genetically investigate a consanguineous family with nonsyndromic postaxial polydactyly.
• To identify the causative gene and specific variant responsible for PAP in this family.
• To contribute to the understanding of PAP genetics, particularly in the Pakistani population.

Main Methods:

• Clinical evaluation of affected individuals in a consanguineous family.
• Genotyping using polymorphic microsatellite markers to establish chromosomal linkage.
• Sequence analysis of candidate genes, specifically KIAA0825, to identify causative variants.

Main Results:

• Linkage was established to chromosome 5q15, harboring the KIAA0825 gene.
• A novel frameshift variant (c.143delG, p.(Cys48Serfs*28)) in KIAA0825 was identified, leading to a premature stop codon.
• This represents the fourth reported variant in KIAA0825 associated with postaxial polydactyly type A10 (PAPA10).

Conclusions:

• The identified KIAA0825 variant is causative of nonsyndromic postaxial polydactyly in the studied family.
• This finding expands the spectrum of KIAA0825 mutations associated with PAP.
• Genetic identification of PAP-causative variants is crucial for accurate diagnosis and genetic counseling in affected populations.