Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly

Abstract

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.