Mutational Screening of GLI3, SHH, and SHH ZRS in 78 Chinese Children with Nonsyndromic Polydactyly

Genet Test Mol Biomarkers. 2018 Sep;22(9):577-581. doi: 10.1089/gtmb.2018.0096.

Abstract

Background: Polydactyly is one of the most common congenital limb abnormalities. Our objective was to identify the genetic causes of non-syndromic polydactyly in 78 Chinese children.

Materials and methods: Genomic DNA was isolated from 78 independent nonsyndromic polydactyly patients, of whom 71 had preaxial polydactyly (PPD), six had postaxial polydactyly (PAP), and one showed combined PPD1 and PAP-A/B. The coding areas and exon/intron boundaries of the GLI3 and SHH genes and the genomic region of SHH ZRS were amplified by polymerase chain reaction and sequenced.

Results: The patient with combined PPD1 and PAP-A/B (subject DUO36) exhibited a heterozygous nonsense mutation in chr7: 42004164G>A (ENST00000395925, c.4507C>T, p.Gln1503Stop ) of the GLI3 gene that has not been previously recorded. We did not detect any mutations in GLI3, SHH, or SHH ZRS in the other 77 nonsyndromic polydactyly patients.

Conclusion: The novel mutation in GLI3 c.4507C>T is likely one of the causes of the PAP and PPD1 of subject DUO36. This important finding should facilitate the optimization of genetic testing for nonsyndromic polydactyly.

Keywords: GLI3; SHH; SHH ZRS; nonsyndromic polydactyly.

MeSH terms

  • Adolescent
  • Asian People / genetics
  • Base Sequence
  • Child
  • Child, Preschool
  • China
  • Female
  • Fingers / abnormalities
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Genotype
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism
  • Humans
  • Limb Deformities, Congenital / genetics
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Pedigree
  • Phenotype
  • Polydactyly / genetics*
  • Thumb / abnormalities
  • Toes / abnormalities
  • Zinc Finger Protein Gli3 / genetics*
  • Zinc Finger Protein Gli3 / metabolism

Substances

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

Supplementary concepts

  • Polydactyly preaxial type 1
  • Polydactyly, Postaxial