中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (2): 192-199.doi: 10.12307/2022.931

• 软骨组织构建 cartilage tissue construction • 上一篇    下一篇

全外显子测序盘状半月板的病因学分析

张  键，林坚平，周  钢，王本超，吴永昌   

  1. 海南医学院附属海南医院(海南省人民医院)关节外科，海南省海口市  570311
  • 收稿日期:2021-11-18 接受日期:2021-12-22 出版日期:2023-01-18 发布日期:2022-06-18
  • 通讯作者: 林坚平，主任医师，硕士生导师，海南医学院附属海南医院(海南省人民医院)关节外科，海南省海口市 570311
  • 作者简介:张键，男，1996年生，海南省屯昌县人，汉族，海南医学院在读硕士，医师，主要从事骨外科方面的研究。
  • 基金资助:
    海南省重点研发任务计划(ZDYF2017112),项目负责人：林坚平；海南医学院研究生创新创业项目(HYYS2020-36)，项目负责人：张键

Etiological analysis of discoid meniscus based on whole exome sequencing

Zhang Jian, Lin Jianping, Zhou Gang, Wang Benchao, Wu Yongchang   

  1. Department of Joint Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, Hainan Province, China
  • Received:2021-11-18 Accepted:2021-12-22 Online:2023-01-18 Published:2022-06-18
  • Contact: Lin Jianping, Master’s supervisor, Chief physician, Department of Joint Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, Hainan Province, China
  • About author:Zhang Jian, Master candidate, Physician, Department of Joint Surgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou 570311, Hainan Province, China
  • Supported by:
    Hainan Province Key Research and Development Task Plan, No. ZDYF2017112 (to LJP); Graduate Innovation and Entrepreneurship of Hainan Medical University, No. HYYS2020-36 (to ZJ)

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摘要：

文题释义：
全外显子测序：外显子是基因在mRNA剪切后保留的片段，与疾病或性状表型改变相关的变异大多来源于外显子，全外显子捕获测序主要针对外显子区域及部分调控区域，可以高效率、高精度筛选致病基因和易感基因。
盘状半月板：外观似圆盘状，是一种先天性半月板畸形，目前病因尚不明确，其形态学改变往往伴随膝关节活动稳定性缺失，因此盘状半月板易于在膝关节活动时发生损伤。

背景：盘状半月板是一种半月板形态学改变，至今发病机制不明，目前尚无关于盘状半月板的基因组学研究。 
目的：通过外显子测序结合生物信息学分析筛选盘状半月板可疑致病基因。
方法：提取7例盘状半月板患者的外周血DNA，分别建库后进行全外显子测序，测序数据与公共基因组数据库对比筛选变异位点，并进行可疑致病突变注释及解读。
结果与结论：① 7例患者共筛选出变异位点6 943个，其中错义突变3 620个，同义突变732个，剪接位点附近的突变488个，剪接位点突变45个，外显子重复20个，外显子缺失84个，非移码突变136个，截断突变54个，延长突变5个，起始位点突变8个；②基于共有突变基因和公共基因数据库筛选出可疑致病基因6个，分别为PADI4、FLNB、SYNE1、COL11A2、COL2A1、MYO9A，包含变异位点15个，结合突变频率数据库、蛋白危害性分析结果和国内外相关研究确定盘状半月板可疑基因为PADI4、FLNB 、SYNE1、COL11A2、COL2A1。

https://orcid.org/0000-0002-7664-9741 (张键)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 盘状半月板, 全外显子测序, 病因学, 发病机制, 基因组学

Abstract: BACKGROUND: Discoid meniscus is a morphological change of the meniscus and its pathogenesis is unknown. There is yet no genomics research on discoid meniscus.
OBJECTIVE: To screen the suspected pathogenic genes of discoid meniscus using whole exome sequencing combined with bioinformatics analysis methods.
METHODS: The peripheral blood DNA of seven patients with discoid meniscus was extracted, and the whole exome sequencing was performed after the DNA database was established. The sequencing data were compared with the public genome database to screen the mutation sites, and the suspicious pathogenic mutations were annotated and interpreted.
RESULTS AND CONCLUSION: A total of 6 943 mutation sites were identified in 7 patients, including 3 620 missense mutations, 732 synonymous mutations, 488 mutations near the splice site, 45 splice site mutations, 20 exon duplications, 84 exon deletions, 136 non-frameshift mutations, 54 truncation mutations, 5 extension mutations, and 8 start site mutations. Based on shared mutation genes and public genomic databases, 6 suspected pathogenic genes, PADI4, FLNB, SYNE1, COL11A2, COL2A1, and MYO9A, were identified, including 15 mutation sites. Combined with mutation frequency database, protein hazard analysis results and related studies have determined that the suspected genes of this disease are PADI4, FLNB, SYNE1, COL11A2, and COL2A1.

Key words: discoid meniscus, whole exome sequencing, etiology, pathogenesis, genomics

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