Targeted exome sequencing reveals a novel GLI3 mutation in a Chinese family with nonsyndromic polydactyly

Dev Dyn. 2019 Oct;248(10):942-947. doi: 10.1002/dvdy.89. Epub 2019 Jul 24.

Abstract

Background: Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial, postaxial, and central subtypes. The aim of this study was to identify genetically pathogenic factor in a Chinese nonsyndromic polydactyly family.

Results: Seven family members and 100 healthy controls were recruited, and the genetically pathogenic factor of the polydactyly family was investigated by targeted exome sequencing. Targeted exome sequencing revealed a novel frameshift mutation c.2148delA (p.Gln716Hisfs*17) of GLI3 in the family. This GLI3 variant was absent in 100 healthy controls and predicted to be highly damaging to the function of the GLI3 by causing half truncation of the protein.

Conclusion: This novel variant extended the mutational and phenotypic spectra of GLI3 and demonstrated the feasibility of targeted exome sequencing in clinical application of molecular diagnosis.

Keywords: GLI3; frameshift mutation; genotype; phenotype; polydactyly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Case-Control Studies
  • Exome / genetics*
  • Family
  • Female
  • Frameshift Mutation*
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • Polydactyly / genetics*
  • Sequence Analysis, DNA / methods
  • Zinc Finger Protein Gli3 / genetics*

Substances

  • GLI3 protein, human
  • Nerve Tissue Proteins
  • Zinc Finger Protein Gli3