Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly

J Orthop Surg Res. 2024 Jul 30;19(1):449. doi: 10.1186/s13018-024-04928-0.

Abstract

Background: Polydactyly is a prevalent congenital anomaly with an incidence of 2.14 per 1000 live births in China. GLI family zinc finger 3 (GLI3) is a classical causative gene of polydactyly, and serves as a pivotal transcription factor in the hedgehog signaling pathway, regulating the development of the anterior-posterior axis in limbs.

Methods: Three pedigrees of polydactyly patients were enrolled from Hunan Province, China. Pathogenic variants were identified by whole-exome sequencing (WES) and Sanger sequencing.

Results: Three variants in GLI3 were identified in three unrelated families, including a novel deletion variant (c.1372del, p.Thr458GlnfsTer44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.Ser656Ter), and a nonsense variant (c.2374 C > T, p.Arg792Ter). These variants were present exclusively in patients but not in healthy individuals.

Conclusions: We identified three pathogenic GLI3 variants in polydactyly patients, broadening the genetic spectrum of GLI3 and contributing significantly to genetic counseling and diagnosis for polydactyly.

Keywords: GLI3; Greig cephalopolysyndactyly syndrome; Isolated polydactyly; Polydactyly; Truncated variant.

MeSH terms

  • Exome Sequencing
  • Female
  • Humans
  • Male
  • Mutation
  • Nerve Tissue Proteins* / genetics
  • Pedigree*
  • Polydactyly* / genetics
  • Zinc Finger Protein Gli3* / genetics

Substances

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