Exome sequencing reveals a novel nonsense mutation of GLI3 in a Chinese family with 'non-syndromic' pre-axial polydactyly.
Polydactyly is a clinically and genetically heterogeneous disorder. In the current report, we present a five-generation Chinese family with non-syndromic pre-axial polydactyly with thumb polydactyly (pre-axial polydactyly type I (PPD-I)) as a major clinical feature. Using whole-exome sequencing (WES), a novel nonsense mutation c.714T>A (p.Y238*) of the glioma-associated oncogene family zinc-finger 3 gene (GLI3) was identified as the pathogenic mutation for this family. Our study has, for the first time, suggested the possible contribution of GLI3 in the patheogenesis of PPD-I, and demonstrated that WES provided an applicable diagnostic tool for identifying mutations in disorders with highly genetical heterogeneity such as polydactyly.
Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ying
Y
Xiang
Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhigang
Z
Wang
Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jingxia
J
Bian
Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yunlan
Y
Xu
Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qihua
Q
Fu
D002681:China; D018389:Codon, Nonsense; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017689:Polydactyly / Q000175:diagnosis* / Q000235:genetics*; D013933:Thumb / Q000002:abnormalities*; D000074290:Zinc Finger Protein Gli3
D018389:Codon, Nonsense; C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3