鉴定与多指畸形相关的 GLI 家族锌指蛋白 3 (GLI3)的截断变异体。
Identification of truncated variants in GLI family zinc finger 3 (GLI3) associated with polydactyly.
机构信息
Department of Hand and Microsurgery, Xiangya Hospital, Central South University, Changsha, 410000, China.
School of Life Sciences, Central South University, Changsha, 410000, China.
出版信息
J Orthop Surg Res. 2024 Jul 30;19(1):449. doi: 10.1186/s13018-024-04928-0.
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.
背景
多指症是一种常见的先天性畸形，在中国的发病率为每 1000 例活产儿中有 2.14 例。GLI 家族锌指 3（GLI3）是多指症的经典致病基因，作为 hedgehog 信号通路中的关键转录因子，调节肢体前后轴的发育。
方法
从中国湖南省招募了三个多指症患者家系。通过全外显子组测序（WES）和 Sanger 测序鉴定致病变异。
结果
在三个不相关的家庭中发现了 GLI3 的三个变异，包括一个新的缺失变异（c.1372del，p.Thr458GlnfsTer44），一个新的插入缺失（indel）变异（c.1967_1968delinsAA，p.Ser656Ter）和一个无义变异（c.2374C>T，p.Arg792Ter）。这些变异仅存在于患者中，而不存在于健康个体中。
结论
我们在多指症患者中鉴定了三个致病性 GLI3 变异，拓宽了 GLI3 的遗传谱，对多指症的遗传咨询和诊断有重要贡献。
Zotero 插件