PDF(Pubmed)
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.
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.
摘要：
背景：多指畸形是一种普遍的先天性畸形，在中国每1000例活产中有2.14例。GLI家族锌指3（GLI3）是多指的经典致病基因，并作为刺猬信号通路中的关键转录因子，调节四肢前后轴的发育。
方法：选取湖南省3家多指患者，中国。通过全外显子组测序(WES)和Sanger测序鉴定致病变体。
结果：在三个不相关的家族中鉴定出GLI3的三个变异体，包括一个新的缺失变体(c.1372del，p.Thr458GlnfsTer44),一个新的插入-删除(indel)变体(c.1967_1968delinsAA，p.Ser656Ter)，和无义变体(c.2374C>T，p.Arg792Ter)。这些变体仅存在于患者中，而不存在于健康个体中。
结论：我们在多指患者中发现了三种致病性GLI3变异，拓宽GLI3的遗传谱，并为多指的遗传咨询和诊断做出重要贡献。
方法：选取湖南省3家多指患者，中国。通过全外显子组测序(WES)和Sanger测序鉴定致病变体。
结果：在三个不相关的家族中鉴定出GLI3的三个变异体，包括一个新的缺失变体(c.1372del，p.Thr458GlnfsTer44),一个新的插入-删除(indel)变体(c.1967_1968delinsAA，p.Ser656Ter)，和无义变体(c.2374C>T，p.Arg792Ter)。这些变体仅存在于患者中，而不存在于健康个体中。
结论：我们在多指患者中发现了三种致病性GLI3变异，拓宽GLI3的遗传谱，并为多指的遗传咨询和诊断做出重要贡献。
