Variants in KIAA0825 underlie autosomal recessive postaxial polydactyly.

Animals Consanguinity Family Health Female Fingers / abnormalities 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 Toes / abnormalities Exome Sequencing / methods

Journal

Human genetics

ISSN: 1432-1203

Titre abrégé: Hum Genet

Pays: Germany

ID NLM: 7613873

Informations de publication

Date de publication:
Jun 2019

Historique:

received: 29 01 2019

accepted: 14 03 2019

pubmed: 15 4 2019

medline: 25 6 2019

entrez: 15 4 2019

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1007/s00439-019-02000-0 PMID: 30982135 PMC: PMC6724712

pubmed: 30982135

doi: 10.1007/s00439-019-02000-0

pii: 10.1007/s00439-019-02000-0

pmc: PMC6724712

mid: NIHMS1024056

doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0

KIAA0825 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

593-600

Subventions

Organisme : NHGRI NIH HHS

ID : U24 HG008956

Pays : United States

Organisme : NHGRI NIH HHS

ID : UM1 HG006493

Pays : United States

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