Novel frame-shift mutations of GLI3 gene in non-syndromic postaxial polydactyly patients.

Abstract

Polydactyly is a common congenital limb deformity. This anomaly may occur in isolation (non-syndromic) or as part of a syndrome. The glioma-associated oncogene family zinc finger 3 (GLI3) is known to be associated with both syndromic and non-syndromic polydactyly. GLI3 plays a predominant role in the pathogenesis of syndromic polydactyly: mutations have been identified in 68% of patients with Greig cephalopolysyndactyly syndrome and 91% of patients with Pallister-Hall syndrome. The knowledge regarding the contribution of GLI3 in non-syndromic polydactyly is currently very limited. In this study, we assembled a cohort of individuals of Chinese ethnicity with non-syndromic postaxial polydactyly. We presented the clinical features and molecular evaluations of 19 probands. GLI3 mutations were identified in 15.8% of probands (3/19) including two novel frame-shift mutations c.3855dupC (p.Met1286HisfsTer18) and c.4141delA (p.Arg1381GlyfsTer38) detected in sporadic cases and one previously reported nonsense mutation (c.1927C>T/p.Arg643Ter) in a familial case. Of note, GLI3 mutations were exclusively detected in patients with bilateral polydactyly affecting both hands and feet. Three out of five (60%) probands with bilateral polydactyly on both hands and feet carried pathogenic mutations in GLI3. Our study demonstrated the role of GLI3 in a significant fraction of patients with non-syndromic bilateral polydactyly affecting both hands and feet.

• Authors: Zhigang Wang, Jian Wang, Yuchan Li, Juan Geng, Qihua Fu, Yunlan Xu, Yiping Shen
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 433 Pg. 195-9 (Jun 10 2014) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 24667698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Base Sequence
• Child
• Child, Preschool
• Female
• Fingers (abnormalities, diagnostic imaging)
• Foot (diagnostic imaging)
• Genotype
• Hand (diagnostic imaging)
• Humans
• Infant
• Kruppel-Like Transcription Factors (genetics)
• Male
• Mutation
• Nerve Tissue Proteins (genetics)
• Phenotype
• Polydactyly (diagnostic imaging, genetics)
• Toes (abnormalities, diagnostic imaging)
• Tomography, X-Ray Computed
• Zinc Finger Protein Gli3