A20单倍体功能不全(HA20)是一种新发现的由TNFAIP3基因突变引起的罕见自身炎症性疾病。HA20在中国人口中很少被记录。在这里,我们报告了来自中国三个无关家庭的8例HA20患者。
2018年至2021年,我们部门诊断出8名中国汉族患者患有HA20。他们的临床数据和基因型被仔细记录和研究。对新鉴定的变体进行了功能验证。我们还对HA20进行了系统的文献综述,并比较了中国人群与其他人群之间HA20的临床特征和基因型。
来自三个家庭的8名HA20患者包括6名成人和2名儿童。有一个男人和七个女人。临床特征包括复发性口腔溃疡(8/8,100%),发烧(4/8,50%),肛周溃疡(3/8,38%),皮损(2/8,25%),关节炎(1/8,13%),和葡萄膜炎(1/8,13%)。三种TNFAIP3变体,A547T,c.1906+2T>G,和R271X,已确定。两个新颖的变体,A547T和c.1906+2T>G,在我们的研究中被证实是致病的。在文献综述中,共纳入了35篇文章报道的126例HA20患者。中国HA20患者的临床表型与其他人群的患者相似,只是生殖器溃疡的发生率较低(16.7%vs.54.4%,p<0.01)。在126例患者中,约有三分之一可检测到自身抗体,其中ANA和抗甲状腺抗体常见。
表型的稀有性和多样性使HA20的诊断对医生来说是一个巨大的挑战。HA20应考虑在儿童发病患者的表现类似于Behçet综合征,尤其是那些家庭成员有类似症状的人。基因检测对HA20的诊断至关重要。两个新的TNFAIP3变体,A547T和c.1906+2T>G,在这项研究中确定。
UNASSIGNED: Haploinsufficiency of A20 (HA20) is a newly described rare autoinflammatory disease caused by TNFAIP3 gene mutations. HA20 has seldom been documented in the Chinese population. Herein, we report eight patients with HA20 from three unrelated families in China.
UNASSIGNED: Eight Chinese Han patients were diagnosed with HA20 in our department from 2018 to 2021. Their clinical data and genotypes were carefully documented and studied. The newly identified variants were functionally verified. We also conducted a systematic literature review of HA20, and the clinical characteristics and genotype of HA20 between the Chinese population and other populations were compared.
UNASSIGNED: Eight HA20 patients from three families comprised six adults and two children. There was one man and seven women. The clinical characteristics included recurrent oral ulcers (8/8, 100%), fever (4/8, 50%), perianal ulcer (3/8, 38%), skin lesions (2/8, 25%), arthritis (1/8, 13%), and uveitis (1/8, 13%). Three TNFAIP3 variants, A547T, c.1906+2T>G, and R271X, were identified. Two novel variants, A547T and c.1906+2T>G, were validated to be pathogenic in our study. In a literature review a total of 126 patients with HA20 reported by 35 articles were included. The clinical phenotype of Chinese HA20 patients was similar to that of patients from other populations except for a lower frequency of genital ulcers (16.7% vs. 54.4%, p < 0.01). Autoantibodies were detectable in approximately one-third of the 126 patients, among which ANA and anti-thyroid antibodies were commonly seen.
UNASSIGNED: The rarity and diversity of phenotypes make the diagnosis of HA20 a huge challenge to physicians. HA20 should be considered in child-onset patients with manifestations that resemble Behçet\'s syndrome, especially those whose family members have similar symptoms. Gene testing is critically helpful for the diagnosis of HA20. Two novel TNFAIP3 variants, A547T and c.1906+2T>G, were identified in this study.