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Source publication
Background:
Polydactyly is a common congenital malformation characterized by the presence of supernumerary fingers or toes. In this case study, we sought to identify the causative pathogenic factor in a family from a northern region of China affected by non-syndromic postaxial polydactyly (PAP).
Methods:
After recruiting a three-generation famil...
Citations
... The ZFN domain enables GLI3 to bind to DNA promoters, suppressing or activating the transcription of SHH target genes. Moreover, the CS domain allows GLI3 to be cleaved from GLI3-A to GLI3-R by the proteasome (19)(20)(21)(22). In this study, we identi ed three GLI3 variants (c.1372del, p.T458QfsX44, c.1967_1968delinsAA, p.S656X, and c.2374C > T, p.R792X) in polydactyly patients. ...
Background
Polydactyly is a prevalent congenital anomaly with an incidence of 0.3–3.6 per 1000 live births. GLI family zinc finger 3 (GLI3) is a classical causative gene of polydactyly, and serves as a pivotal transcription factor in the hedgehog signaling pathway, regulating the development of the anterior-posterior axis in limbs.
Methods
Three pedigrees of polydactyly patients were enrolled from Hunan Province, China. Pathogenic variants were identified by whole-exome sequencing (WES) and Sanger sequencing.
Results
Three variants of GLI3 were identified in these three families, including a novel deletion variant (c.1372del, p.T458QfsX44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.S656X), and a nonsense variant (c.2374C > T, p.R792X). These variants were present exclusively in patients but not in healthy individuals.
Conclusions
We identified three pathogenic GLI3 variants in polydactyly patients, broadening the genetic spectrum of GLI3 and contributing significantly to genetic counseling and diagnosis for polydactyly.
Background
GLI3 gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister–Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated GLI3 mutations are rare. In this study, a novel GLI3 mutation was identified in a Chinese family with IPD.
Results
We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the GLI3 gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family.
Conclusions
The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and GLI3 and expands the previously established spectrum of GLI3 mutations and associated phenotypes.
