COL3A1基因新突变导致血管型Ehlers-Danlos综合征一家系的临床特征与遗传学分析

Clinical characteristics and genetic analysis of a pedigree with vascular Ehlers-Danlos syndrome caused by a novel mutation in COL3A1 gene

患者男,27岁,因“无明显诱因出现剧烈胸痛伴心悸、气短、胸闷”于2018年8月收治入西京医院。计算机断层扫描血管造影检查结果提示主动脉A型夹层。基于二代测序的遗传性主动脉疾病相关的15个基因的组合检测及Sanger测序验证发现患者COL3A1基因存在c.998G>T(p.Gly333Val)杂合错义突变。通过家系成员的Sanger测序验证,突变c.998G>T与该家系患者表型共分离。根据ACMG遗传变异分类标准与指南判读,该突变致病等级为“可能致病”,携带该突变可明确诊断为“血管型Ehlers-Danlos综合征”。明确诊断后,对患者进行了对症治疗,但病情发展迅速,患者放弃治疗,出院后不久死亡。本研究报道了1个COL3A1基因的新突变,扩展了该基因的突变谱。

A 27-year-old male was admitted to the Xijing Hospital in August 2018 due to unprovoked severe thoracodynia with palpitations,shortness of breath and chest tightness.Computed tomography angiography showed a type A aortic dissection.Genetic testing based on next-generation sequencing for 15 genes associated with hereditary aortic diseases and Sanger sequencing validation revealed a heterozygous missense mutation c.998G>T(p.Gly333Val)in the COL3A1 gene.Sanger sequencing verification of family members confirmed that the mutation c.998G>T co-segregated with the patient′s phenotype in this family.That mutation was classified as"likely pathogenic"according to American College of Medical Genetics and Genomics standards and guidelines for genetic variant classification.Carriers of this mutation can be definitively diagnosed with"vascular Ehlers-Danlos syndrome".After the diagnosis was clarified,symptomatic treatment was given to the patient,but the disease progressed rapidly.The patient discontinued treatment and died shortly after being discharged.In this study,we found a new variant in the COL3A1 gene,expanding the mutation spectrum of this gene.