A20单倍体不足临床特征与基因型表型的关联

Relationship clinical manifestations and genotype-phenotype in patients with A20 haploinsufficiency

目的探讨A20单倍体不足(HA20)临床特征与基因型表型的关联性,以及HA20与白塞综合征(Beh9et’s syndrome,BS)临床特征的差异。方法在PubMed和CNKI使用关键词“haploinsufficiency A20”或“TNFAIP3”检索2016-01-01至2021-12-31报道的HA20文献(中文及英文),纳入有完整资料的HA20患者。按照HA20基因型不同分为7号外显子组和非7号外显子组,比较两组之间临床表型的差异。同时比较HA20与BS人群的异同,BS队列选自中国人群且资料较完整的患者队列。结果共纳入38篇文章126例HA20患者,符合基因型比较入排标准的HA20共120例,男女比例为2∶3,中位年龄18(IQR 0~71)岁,起病中位年龄6(IQR 0~29)岁。携带7号外显子变异的患者外阴溃疡发生率低于携带非7号外显子变异者(25.0%vs.51.2%,P=0.018)。比较HA20(n=126)与BS(n=489)两组患者,发现HA20患者起病中位年龄低于BS患者[6(0~29)岁vs.25(18-33)岁],HA20患者胃肠道受累(56.3%vs.15.1%)、皮肤病变(35.7%vs.14.1%)以及关节炎(30.2%vs.8.4%)较BS更常见(P<0.001),而口腔溃疡(79.4%vs.96.3%)、外阴溃疡(43.7%vs.71.2%)、眼炎(7.9%vs.24.1%)及血管受累(7.1%vs.25.4%)发生率则低于BS患者(P<0.001)。结论携带7号外显子变异的HA20者较少出现外阴溃疡。HA20较BS发病年龄更早,更易出现胃肠道病变、皮肤病变及外周关节炎。

Objective To explore the manifestations of A20 haploinsufficiency(HA20),genotype-phenotype relationship,and the differences in clinical features between HA20 and Beh et’s syndrome(BS).Methods We searched PubMed and CNKI using the terms‘TNFAIP3’and‘A20 haploinsufficiency’for literature both in Chinese and English through January 2016 to December 2021,and HA20 patients with complete data were included.HA20 patients were divided into exon 7 and non-exon 7 groups according to their genotype,and the clinical phenotypes were compared.Also,clinical manifestations were compared between HA20 and BS patients who were enrolled in a Chinese cohort.Results A total of 126 HA20 patients from 38 articles were included,and a total of 120 HA20 cases met the genotype comparison entry row criteria,with a male to female ratio of 2∶3,median age 18(0-71)years old,and median age of onset 6(0-29)years old.HA20 patients carrying exon 7 variants had a lower incidence of vulvar ulceration than that in patients with non-exon 7 variants(25.0%vs.51.2%,P=0.018).Comparing patients with HA20(n=126)and BS(n=489),we found that the median age of onset was lower in HA20[6(0-29)years old vs.25(18-33)years old],and the incidence of gastrointestinal involvement(56.3%vs.15.1%),skin involvement(35.7%vs.14.1%),and arthritis(30.2%vs.8.4%)were more common in HA20 patients than those in BS(P<0.001),while oral ulcers(79.4%vs.96.3%),vulvar ulcers(43.7%vs.71.2%),ophthalmia(7.9%vs.24.1%),and vascular involvement(7.1%vs.25.4%)occurred less frequently(P<0.001).Conclusions HA20 patients carrying non-exon 7 variants have a lower incidence of vulvar ulceration.When compared with BS,HA20 has an earlier onset age,more prone to gastrointestinal tract involvement,skin involvement and arthritis.