组织工程与重建外科杂志

组织工程与重建外科杂志 ›› 2022, Vol. 18 ›› Issue (3): 209-.

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一种基于DNA测序结果的静脉/淋巴管畸形新基因分型

  

  • 出版日期:2022-06-01 发布日期:2022-07-11

Sequencing analysis on tissue DNA from 55 patients with venous

malformations and lymphatic malformations　

  • Online:2022-06-01 Published:2022-07-11

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摘要： 目的　明确静脉/淋巴管畸形的突变基因并进行基因诊断分型。方法　采用二代高通量测序技术，对55例确诊静脉/淋巴管畸形患者的组织样本进行DNA的靶向捕获二代测序和生物信息学分析，对外显子区域和部分内含子区域进行检测，主要检测点突变和插入/缺失突变。结果　55例诊断为静脉/淋巴管畸形患者共采集55个组织样本，经过生物信息学分析和筛选后共发现3种潜在致病基因、15个变异位点，主要突变的基因是TEK和PIK3CA。TEK最常见的突变位点是L914F，单纯TEK突变中86.67%为单纯静脉畸形，100%伴有静脉畸形成分。PIK3CA最常见的突变位点是E542K和E545K。单纯PIK3CA突变中52.63%为血管骨肥大综合征，21.05%为单纯淋巴管畸形，94.74%伴有淋巴管畸形成分。根据基因检测结果，静脉/淋巴管畸形可以分为TEK突变型、PIK3CA突变型、双突变型和无突变型。结论　明确了TEK和PIK3CA是静脉/淋巴管畸形的主要突变基因，据此可将基因分型为TEK突变型、PIK3CA突变型、双突变型和无突变型。基因检测能够预判病灶是否存在静脉畸形或淋巴管畸形成分。

关键词: 脉管畸形, 　二代测序, 　基因分型, 　精准医疗

Abstract: Objective　To identify the mutations in the tissue DNA from patients with venous malformations or lymphatic malformations and to conduct genotyping for genetic diagnosis. Methods　Based on the next-generation sequencing, 55 tissues from different patients diagnosed as venous malformations or lymphatic malformations were analyzed. The tissues were sequenced in the exons area and part of the introns area of a customized panel for 2 types of mutations (point mutation and loss/insert of small fragments). Results　All 55 samples from 55 patients were collected and analyzed. Three probably driven mutations including 15 variable sites were identified. The most frequently mutated gene was TEK and PIK3CA. The most frequent variable site of TEK was L914F, and for PIK3CA were E542K and E545K. In patients whose tissues were detected as TEK mutations, 86.67% were venous malformations, and 100% involved venous malformation, while in those whose tissues were detected as PIK3CA mutations, 52.63% were KTS, 21.05% were lymphatic malformations and 94.74% involved lymphatic malformation. According to the genetic results, venous malformations and lymphatic malformations can be classified as TEK type, PIK3CA type, double mutations type, and non-mutation type. Conclusion　Gene mutations can be detected in venous malformations or lymphatic malformations. Venous malformations and lymphatic malformations can be classified as
TEK type, PIK3CA type, double mutations type, and non-mutation type. Gene tests can provide evidence of lesions involving venous malformation or lymphatic malformations.

Key words: Vascular malformation, 　Next-generation sequencing, 　Genotyping, 　Precision medicine