Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly

Hum Genet. 2019 Jun;138(6):593-600. doi: 10.1007/s00439-019-02000-0. Epub 2019 Apr 13.


Postaxial polydactyly (PAP) is a common limb malformation that often leads to cosmetic and functional complications. Molecular evaluation of polydactyly can serve as a tool to elucidate genetic and signaling pathways that regulate limb development, specifically, the anterior-posterior specification of the limb. To date, only five genes have been identified for nonsyndromic PAP: FAM92A, GLI1, GLI3, IQCE and ZNF141. In this study, two Pakistani multiplex consanguineous families with autosomal recessive nonsyndromic PAP were clinically and molecularly evaluated. From both pedigrees, a DNA sample from an affected member underwent exome sequencing. In each family, we identified a segregating frameshift (c.591dupA [p.(Q198Tfs*21)]) and nonsense variant (c.2173A > T [p.(K725*)]) in KIAA0825 (also known as C5orf36). Although KIAA0825 encodes a protein of unknown function, it has been demonstrated that its murine ortholog is expressed during limb development. Our data contribute to the establishment of a catalog of genes important in limb patterning, which can aid in diagnosis and obtaining a better understanding of the biology of polydactyly.

MeSH terms

  • Animals
  • Consanguinity
  • Exome Sequencing / methods
  • Family Health
  • Female
  • Fingers / abnormalities*
  • Fingers / pathology
  • Genes, Recessive / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mice, Inbred C57BL
  • Mutation*
  • Pedigree
  • Phenotype
  • Polydactyly / genetics*
  • Polydactyly / pathology
  • Toes / abnormalities*
  • Toes / pathology


  • Intracellular Signaling Peptides and Proteins
  • KIAA0825 protein, human

Supplementary concepts

  • Polydactyly, Postaxial