Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (PUMCH); Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.
Department of Rheumatology, The Second Affiliated Hospital of Dalian Medical University; Key Laboratory of Autoantibody Detection of Dalian, Dalian, China.
Front Immunol. 2022 Jul 26;13:955079. doi: 10.3389/fimmu.2022.955079. eCollection 2022.
Haploinsufficiency of A20 (HA20) is a newly described rare autoinflammatory disease caused by gene mutations. HA20 has seldom been documented in the Chinese population. Herein, we report eight patients with HA20 from three unrelated families in China.
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.
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 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.
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 variants, A547T and c.1906+2T>G, were identified in this study.
A20（HA20）单倍体不足是一种新描述的罕见自身炎症性疾病，由 基因突变引起。HA20 在中国人群中很少有报道。本文报道了来自中国三个无关家庭的 8 例 HA20 患者。
2018 年至 2021 年，我们在科室诊断了 8 例汉族 HA20 患者。仔细记录并研究了他们的临床资料和基因型。对新发现的变异进行了功能验证。我们还对 HA20 进行了系统的文献回顾，并比较了中国人群与其他人群 HA20 的临床特征和基因型。
来自三个家庭的 8 例 HA20 患者包括 6 例成人和 2 例儿童，其中男性 1 例，女性 7 例。临床特征包括复发性口腔溃疡（8/8，100%）、发热（4/8，50%）、肛周溃疡（3/8，38%）、皮肤损伤（2/8，25%）、关节炎（1/8，13%）和葡萄膜炎（1/8，13%）。发现 3 个变异，A547T、c.1906+2T>G 和 R271X。我们的研究验证了两个新的变异，A547T 和 c.1906+2T>G，为致病性变异。文献综述共纳入 35 篇文章报道的 126 例 HA20 患者。除生殖器溃疡频率较低（16.7%比 54.4%，p<0.01）外，中国 HA20 患者的临床表型与其他人群相似。大约三分之一的 126 例患者可检测到自身抗体，其中抗核抗体和抗甲状腺抗体常见。
表型的罕见性和多样性使得 HA20 的诊断对医生来说极具挑战。对于表现类似于贝切特综合征的儿童发病患者，尤其是其家庭成员有类似症状的患者，应考虑 HA20。基因检测对 HA20 的诊断至关重要。本研究发现了两个新的 变异，A547T 和 c.1906+2T>G。
