摘要目的:对1例疑似先天性挛缩蜘蛛指畸形患者进行变异筛查，探讨其可能的分子遗传学发病机制，为临床诊断提供依据。方法:应用全外显子测序技术筛查基因变异。候选致病基因剪接位点变异经Sanger测序验证后，经RT-PCR、TA克隆测序确定新转录本序列。结果:患者 FBN2基因存在c.533-1G>C杂合变异，未见报道。mRNA测序显示该变异导致 FBN2基因原剪接受位消失的同时，激活c.533-71处潜在剪接受位位点，由此产生的新转录本中插入了70bp序列。推测新转录本编码多肽在氨基酸179位由缬氨酸(Val)变成丝氨酸(Ser)，并移码26位后终止(p.Val179Serfs26*)。根据美国医学遗传学与基因组学学会指南， FBN2基因c.533-1G>C变异判定为致病性变异(PVS1+PM2+PP3)。 结论:FBN2基因c.533-1G>C变异引起新转录本发生功能丧失性变异，可导致先天性挛缩蜘蛛指畸形。

abstractsObjective:To identify the pathogenic variants from a patient with suspected congenital contractural arachnodactyly, and to explore the possible molecular genetic pathogenesis, so as to provide evidence for clinical diagnosis.Methods:Whole exome sequencing was performed for the patient. The splicing site variation of candidate pathogenic genes was verified by Sanger sequencing, and the new transcript sequence was determined by RT-PCR and TA-cloning sequencing.Results:The patient carried a heterozygous c. 533-1G>C variant of FBN2 gene, which was not reported. The sequencing of mRNA showed that the variant leaded to the disappearance of the canonical splice acceptor site of FBN2 gene and the activation of a cryptic splice acceptor site at c. 533-71, resulting in the insertion of 70 bp sequence in the new transcript. It was speculated that the polypeptide encoded by the new transcript changed from valine (Val) to serine (Ser) at amino acid 179, and prematurely terminated after 26 aminoacids.According to the guidelines of American College of Medical Genetics and Genomics, the variant of FBN2 gene c. 533-1G>C was determined as pathogenic (PVS1+ PM2+ PP3 ). Conclusion:A novel splicing variant of FBN2 gene (c.533-1G>C) was identified, which can lead to congenital contractural arachnodactyly.