Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly.

TitleVariants in KIAA0825 underlie autosomal recessive postaxial polydactyly.
Publication TypeJournal Article
Year of Publication2019
AuthorsUllah, I, Kakar, N, Schrauwen, I, Hussain, S, Chakchouk, I, Liaqat, K, Acharya, A, Wasif, N, Santos-Cortez, RLyn P, Khan, S, Aziz, A, Lee, K, Couthouis, J, Horn, D, Kragesteen, BK, Spielmann, M, Thiele, H, Nickerson, DA, Bamshad, MJ, Gitler, AD, Ahmad, J, Ansar, M, Borck, G, Ahmad, W, Leal, SM
JournalHum Genet
Date Published2019 Jun
KeywordsAnimals, Consanguinity, Family Health, Female, Fingers, Genes, Recessive, Genetic Predisposition to Disease, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Mice, Inbred C57BL, Mutation, Pedigree, Phenotype, Polydactyly, Toes, Whole Exome Sequencing

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.

Alternate JournalHum. Genet.
PubMed ID30982135
PubMed Central IDPMC6724712
Grant ListU24 HG008956 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States