title: 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.affiliation: Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China; Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China. Electronic address: xu.yunlan@hotmail.com.
authors.forename: Yunlan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, PR China; Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: yiping.shen@childrens.harvard.edu.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005528:Foot / Q000000981:diagnostic imaging; D005838:Genotype; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D007223:Infant; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017689:Polydactyly / Q000000981:diagnostic imaging / Q000235:genetics*; D014034:Toes / Q000002:abnormalities* / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D000074290:Zinc Finger Protein Gli3
chemical_list: C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3
keywords: Frame-shift mutations; GLI3 gene; Non-syndromic polydactyly; Postaxial polydactyly