第二代测序法对SLE家系患者致病基因的筛选研究（英文）

【作者】 武永康； 王圣洁；

【机构】 四川大学华西医院；

【摘要】 Purpose: Gene abnormal mutations play a prominent role in the prevalence of Systemic lupus erythematous(SLE) in a specific family, which is also necessary for occurrence and development of SLE and its subtypes. This study was undertaken to select main pathogenic genes for a SLE family with specific immunological characteristics, using next-generation sequencing(NGS) to sequence the entire exon that contribute to provide theoretical basis for the individualized diagnosis and treatment of SLE. Methods: One SLE family collected in Sichuan Province, China, with the special immunological features(all patients expressed higher levels of IgE as well as RF, and positive ANA), suggesting this SLE family belong to a special SLE subtype. This study employed next-generation sequencing(NGS) to sequence the whole exon to screen for candidate genes. Sanger sequencing was used to determine a pathogenic mutation in the SLE family. Gene screening and bioinformatics analysis was used to verify the susceptibility of pure gene mutations to SLE. Results: In total, 44 mutant genes were found in the SLE family by NGS, including 3 insertions(EMG1, WDR66, REC8) and 5 deletions(PKD1 L2, NUMBL, OR2 T27, HAVCR1, USP20). The other 36 genes are SRP72, TLR10, FOCAD, SLC22 A1, CA9, CCNJL, SGSM1, LOXL3, RECK, TMEM17, UPP2, SETX, ANO7, RMND1, OPRM1, PSG9, TMEM173, NEDD4, WDR55, ALDH1 B1, HIF3 A, HELZ2, KDR, HAVCR1, PRR21, HLA-A, TMEM173, IFT74, LIPA, TMEM173, AASDH, KIAA1211, MMP12, EMG1, WDR66, HCAR3, REC8, PKD1 L2, NUMBL, PRAMEF22, OR2 T27, HAVCR1, PRSS3, USP20. rs17524437 of SRP72 was one of the important candidate genes in SLE family patients. t/t mutations were detected in all patients with pure mutations, and there was no significant difference in the distribution frequency of rs17524437 of SRP72 genotype between the patients with scattered SLE and the healthy control group. Conclusions: The role of SRP72 homozygous gene mutations in the pathogenesis of SLE needs to be further increased to verify the number of samples. The use of bioinformatics methods to study the main pathogenic genes and combinations in SLE provides a theoretical basis for the individualized treatment.更多还原

【Abstract】 Purpose: Gene abnormal mutations play a prominent role in the prevalence of Systemic lupus erythematous(SLE) in a specific family, which is also necessary for occurrence and development of SLE and its subtypes. This study was undertaken to select main pathogenic genes for a SLE family with specific immunological characteristics, using next-generation sequencing(NGS) to sequence the entire exon that contribute to provide theoretical basis for the individualized diagnosis and treatment of SLE. Methods: One SLE family collected in Sichuan Province, China, with the special immunological features(all patients expressed higher levels of IgE as well as RF, and positive ANA), suggesting this SLE family belong to a special SLE subtype. This study employed next-generation sequencing(NGS) to sequence the whole exon to screen for candidate genes. Sanger sequencing was used to determine a pathogenic mutation in the SLE family. Gene screening and bioinformatics analysis was used to verify the susceptibility of pure gene mutations to SLE. Results: In total, 44 mutant genes were found in the SLE family by NGS, including 3 insertions(EMG1, WDR66, REC8) and 5 deletions(PKD1 L2, NUMBL, OR2 T27, HAVCR1, USP20). The other 36 genes are SRP72, TLR10, FOCAD, SLC22 A1, CA9, CCNJL, SGSM1, LOXL3, RECK, TMEM17, UPP2, SETX, ANO7, RMND1, OPRM1, PSG9, TMEM173, NEDD4, WDR55, ALDH1 B1, HIF3 A, HELZ2, KDR, HAVCR1, PRR21, HLA-A, TMEM173, IFT74, LIPA, TMEM173, AASDH, KIAA1211, MMP12, EMG1, WDR66, HCAR3, REC8, PKD1 L2, NUMBL, PRAMEF22, OR2 T27, HAVCR1, PRSS3, USP20. rs17524437 of SRP72 was one of the important candidate genes in SLE family patients. t/t mutations were detected in all patients with pure mutations, and there was no significant difference in the distribution frequency of rs17524437 of SRP72 genotype between the patients with scattered SLE and the healthy control group. Conclusions: The role of SRP72 homozygous gene mutations in the pathogenesis of SLE needs to be further increased to verify the number of samples. The use of bioinformatics methods to study the main pathogenic genes and combinations in SLE provides a theoretical basis for the individualized treatment.更多还原