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

• الحاوية / القاعدة: Journal of Orthopaedic Surgery and Research
• المؤلفون الرئيسيون: Run-Yan Wang, Qin Xiong, Si-Hua Chang, Jie-Yuan Jin, Rong Xiang, Lei Zeng, Fang Yu
• التنسيق: مقال
• اللغة: الإنجليزية
• منشور في: BMC 2024-07-01
• الموضوعات: Polydactyly; GLI3; Truncated variant; Isolated polydactyly; Greig cephalopolysyndactyly syndrome
• الوصول للمادة أونلاين: https://doi.org/10.1186/s13018-024-04928-0

Abstract Background Polydactyly is a prevalent congenital anomaly with an incidence of 2.14 per 1000 live births in China. 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 in GLI3 were identified in three unrelated families, including a novel deletion variant (c.1372del, p.Thr458GlnfsTer44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.Ser656Ter), and a nonsense variant (c.2374 C > T, p.Arg792Ter). 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.