叛徒柯林斯综合征(TCS,OMIM:154500)是一种罕见的先天性颅面疾病,由TCOF1,POLR1D,POLR1C,POLR1B关于表型变异性及其相对变异之间关联的研究非常有限。本系统综述了PubMed和Scopus的53篇文献,通过统计分析探讨TCS基因型与表型的潜在相关性。包括报告完整分子遗传学和临床数据的研究。我们确定TCOF1内的分子异常(88.71%)占大多数TCS病例。在外显子24中检测到TCOF1的唯一真实热点,鉴定出复发的c.4369_4373delAAGAA变体。虽然POLR1D的热点,POLR1C,和POLR1B分别在外显子3、8和15中鉴定。我们的结果表明,在携带TCOF1变体而不是POLR1的亚洲患者中可能观察到更高的严重程度。此外,与TCOF1第24外显子内的任何变体相比,常见的5bp缺失倾向于具有更高的严重程度。总之,该报告提示了TCS的遗传和临床数据之间的关系。我们的发现可作为临床诊断和进一步生物学研究的参考。
Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes
TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic
review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within
TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for
TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified. While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of
TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.