MEFV基因变异患者MVK、NLRP3、TNFRSF1A和PSTPIP1基因的新一代测序分析及基因型-表型相关性

IF 1.3 Q4 RHEUMATOLOGY
Gamze Vuran, Afig Berdeli
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引用次数: 0

摘要

目的:在本研究中,我们旨在通过新一代测序方法(NGS)评估其他白细胞介素-1b介导的单基因自身炎症性疾病(AIDs)(肿瘤坏死因子受体-1相关周期综合征、高免疫球蛋白D综合征、低温霉素相关周期综合征(CAPS)、化脓性关节炎、坏疽性脓皮病和痤疮综合征)在临床家族性地中海热症状中未检测到MEFV基因变异的病例。方法:对入选病例及其父母进行访谈和问卷调查。针对MEFV基因分析结果为阴性的病例,研究了白介素-1b介导的艾滋病的靶向基因面板,包括四个基因(MVK、NLRP3、TNFRSF1A和PSTPIP1)。采用靶向NGS方法进行遗传分析。结果:在研究样本中的40例患者中,有16例发现了变异。这些变异仅在变异数据库中报道,其中3个被鉴定为明确致病变异(MVK基因的V377I、TNFRSF1A基因的C52Y和NLRP3基因的I313V), 4个为不确定意义变异(VUS) (TNFRSF1A的R92Q、PSTPIP1的A372V、NLRP3的V198M和Q703K), 1个为良性多态性(MVK基因的S52N)。变异阳性病例的中位发病年龄为10.5(3.5-18)岁。变异阳性组最常见的临床表现是关节痛、发热和腹痛。40例患者中有3例符合遗传分析前的分类标准,但只有1例患者通过遗传分析被诊断为CAPS,其他患者被认为是非特异性表型。结论:NGS基因面板的应用对全身性艾滋病等具有异质临床表现的疾病是有益的。虽然检测到的变异数量很高,但临床诊断率仍然很低。这些疾病的基因型-表型关系尚不清楚。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Next-Generation Sequencing Analysis of MVK, NLRP3, TNFRSF1A, and PSTPIP1 Genes in Patients without MEFV Gene Variation and Genotype-Phenotype Correlation.

Next-Generation Sequencing Analysis of MVK, NLRP3, TNFRSF1A, and PSTPIP1 Genes in Patients without MEFV Gene Variation and Genotype-Phenotype Correlation.

Objective: In this study, we aimed to evaluate other interleukin-1b-mediated monogenic autoinflam- matory diseases (AIDs) (tumor necrosis factor receptor-1-associated periodic syndrome, hyperimmuno- globulin D syndrome, cryopyrin-associated periodic syndrome (CAPS), pyogenic arthritis, pyoderma gangrenosum, and acne syndrome) by the next-generation sequencing method (NGS) in cases with clinical Familial Mediterranean Fever symptoms, and no variant detected in the MEFV gene. Methods: The cases included in this study and their parents were interviewed and filled in a survey form. The targeted genetic panel for interleukin-1b-mediated AIDs covering four genes (MVK, NLRP3,TNFRSF1A, and PSTPIP1) was studied for cases with a negative result from the MEFV gene analysis. The genetic analysis was conducted using the targeted NGS method. Results: Variants were found in 16 out of the 40 patients in the study sample. These variants were pri- orly reported in variant databases, and three of them were identified as definitely pathogenic (V377I of the MVK gene, C52Y of the TNFRSF1A gene, and I313V of the NLRP3 gene), four as a variant of uncer- tain significance (VUS) (R92Q of the TNFRSF1A, A372V of the PSTPIP1, and V198M and Q703K of the NLRP3), and one as benign polymorphism (S52N of the MVK gene). The median age of onset among variant-positive cases was 10.5 (3.5-18) years. The most common clinical findings in the variant-positive group were arthralgia, fever, and abdominal pain. While three out of 40 patients met the classification criteria before genetic analysis, only one patient was diagnosed with CAPS as a result of genetic analy- sis, and other patients were considered as nonspecific phenotype. Conclusion: The use of NGS gene panels seems beneficial in diseases with heterogeneous clinical manifestations such as systemic AIDs. Although the number of variants detected is high, clinical diag- nosis rates remain low. The genotype–phenotype relationship in these diseases is still unclear.

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