A novel frame-shift mutation of GLI3 causes non-syndromic and complex digital anomalies in a Chinese family

Clin Chim Acta. 2011 May 12;412(11-12):1012-7. doi: 10.1016/j.cca.2011.02.007. Epub 2011 Feb 12.


A three-generation Han Chinese family was found with complex digital anomalies including various types of polydactyly and syndactyly of fingers and toes. Some extra digits are composed only of soft tissues while others are complete fingers or toes, making this complex case different from previously reported pedigrees. The digital disease shows an autosomal dominant inheritance model. To locate the causative gene, whole-genome SNP analysis was performed using Illumina 370 K CNV-Quad chips followed by linkage analysis with a self-developed algorithm Haplo2Ped (http://bighapmap.big.ac.cn/software.html). Three candidate regions with the highest signals (LOD scores 2.1070) were identified. In one region from 33,904,914 bp to 45,529,271 bp in chromosome 7, GLI3 was selected for further analysis. PCR sequencing and subsequent clone sequencing revealed a single nucleotide deletion (c.2884delG) in exon 14. This frame shift mutation generated a truncated protein with 40 non-endogenous amino acids in its C-terminal (p.Asp962MetfsX41). GLI3 was previously reported to associate with Greig Cephalopolysyndactyly Syndrome, Pallister-Hall Syndrome, and a few cases of preaxial and postaxial polydactylies. We report for the first time a novel mutation of GLI3 causing various digital abnormalities, including multi symptoms as both polydactyly and syndactyly among affected members but no other body maldevelopments (non-syndromic).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Base Sequence
  • Child
  • Child, Preschool
  • Female
  • Fingers / abnormalities*
  • Frameshift Mutation*
  • Genetic Linkage
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Pedigree*
  • Sequence Deletion
  • Toes / abnormalities*
  • Zinc Finger Protein Gli3


  • GLI3 protein, human
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Zinc Finger Protein Gli3