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Abstract：
BACKGROUND: Haploinsufficiency of A20 (HA20) is a novel genetic disease presented by Zhou et al in 2016. A20 is a protein encoded by TNFAIP3. Loss-of-function mutation in TNFAIP3 will trigger a new autoinflammatory disease: HA20. HA20-affected patients may develop a wide range of clinical manifestations, such as Behcet disease, rheumatoid arthritis, rheumatic fever, juvenile idiopathic arthritis, and systemic lupus erythematosus. HA20 is rarely reported, thus remaining far from thoroughly understood. Sixty-one cases of HA20 have been reported worldwide, among which 29 cases were diagnosed with Behcet disease ultimately. Moreover, 3 cases have been reported in China, which was the first report of HA20 characterized by Behcet disease. A comprehensive understanding of the pathogenic genes of HA20 could help us apply targeted therapy as soon as possible to improve patients\' survival rates.
METHODS: A 2-year-old 3-month-old child was presented to our hospital with recurrent infectious enteritis and stomatitis.
METHODS: Genetic mutations were detected immediately, and a novel pathogenic mutation was found in TNFAIP3. A heterozygous mutation (c.436-437deTC) located at TNFAIP3 was confirmed. The present research indicated that the TNFAIP3 mutation of c.436-437deTC (p.L147Qfs∗7) accounted for familial Behcet-like autoinflammatory syndrome in the child suffering from HA20, while no variation in this locus was found in her parents.
METHODS: Symptomatic treatments including oral administration of prednisone (12.5 mg/d) and iron supplement were performed, and repeated infection was no longer observed in the child. Pain and activity limitation was found in the knee joints. The treatment regimen was adjusted to oral prednisone (12.5 mg/dose, 2 doses/d) and subcutaneous injection of rhTNFR:Fc (12.5 mg/week).Outcomes: At the last follow-up, the limbs\' activities were normal, the inflammatory indicators were reduced or within the normal range. The prednisone dose was reduced to 7.5 mg/d, while the dose of rhTNFR:Fc was not changed.
CONCLUSIONS: We have identified a novel pathogenic HA20 mutation. In this article, 1 case was analyzed in-depth in terms of clinical manifestations of the patient and new sources of such a novel disease, which might improve our understanding of this disease.
METHODS: A 2-year-old 3-month-old child was presented to our hospital with recurrent infectious enteritis and stomatitis.
METHODS: Genetic mutations were detected immediately, and a novel pathogenic mutation was found in TNFAIP3. A heterozygous mutation (c.436-437deTC) located at TNFAIP3 was confirmed. The present research indicated that the TNFAIP3 mutation of c.436-437deTC (p.L147Qfs∗7) accounted for familial Behcet-like autoinflammatory syndrome in the child suffering from HA20, while no variation in this locus was found in her parents.
METHODS: Symptomatic treatments including oral administration of prednisone (12.5 mg/d) and iron supplement were performed, and repeated infection was no longer observed in the child. Pain and activity limitation was found in the knee joints. The treatment regimen was adjusted to oral prednisone (12.5 mg/dose, 2 doses/d) and subcutaneous injection of rhTNFR:Fc (12.5 mg/week).Outcomes: At the last follow-up, the limbs\' activities were normal, the inflammatory indicators were reduced or within the normal range. The prednisone dose was reduced to 7.5 mg/d, while the dose of rhTNFR:Fc was not changed.
CONCLUSIONS: We have identified a novel pathogenic HA20 mutation. In this article, 1 case was analyzed in-depth in terms of clinical manifestations of the patient and new sources of such a novel disease, which might improve our understanding of this disease.
摘要：
背景：A20单倍体功能不全（HA20）是Zhou等人在2016年提出的一种新型遗传病。A20是由TNFAIP3编码的蛋白质。TNFAIP3中的功能丧失突变将引发一种新的自身炎性疾病：HA20。受HA20影响的患者可能会出现广泛的临床表现，比如白塞病，类风湿性关节炎,风湿热,幼年特发性关节炎，和系统性红斑狼疮.HA20很少报道，因此，还远远没有被彻底理解。全球已报告61例HA20，其中29例最终确诊为白塞病。此外，中国已报告3例，这是首次报道以白塞病为特征的HA20。全面了解HA20的致病基因有助于我们尽快应用靶向治疗以提高患者的生存率。
方法：1例3个月大的2岁儿童因复发性感染性肠炎和口腔炎就诊。
方法：立即检测到基因突变，在TNFAIP3中发现了一个新的致病突变。确认了位于TNFAIP3的杂合突变(c.436-437deTC)。本研究表明c.436-437deTC的TNFAIP3突变（p。L147Qfs*7）解释了患有HA20的儿童的家族性Behcet样自身炎症综合征，而在其父母中未发现该位点的变异。
方法：对症治疗包括口服泼尼松（12.5mg/d）和补铁，并且在孩子中不再观察到重复感染。在膝关节中发现疼痛和活动受限。治疗方案调整为口服泼尼松（12.5mg/剂，2剂/天）并皮下注射rhTNFR：Fc（12.5mg/周）。结果:在最后一次随访中，四肢活动正常，炎症指标降低或在正常范围内。泼尼松剂量降至7.5mg/d,而rhTNFR:Fc的剂量没有改变。
结论：我们发现了一种新的致病性HA20突变。在这篇文章中,对1例患者的临床表现和这种新型疾病的新来源进行了深入分析，这可能会提高我们对这种疾病的认识。
方法：1例3个月大的2岁儿童因复发性感染性肠炎和口腔炎就诊。
方法：立即检测到基因突变，在TNFAIP3中发现了一个新的致病突变。确认了位于TNFAIP3的杂合突变(c.436-437deTC)。本研究表明c.436-437deTC的TNFAIP3突变（p。L147Qfs*7）解释了患有HA20的儿童的家族性Behcet样自身炎症综合征，而在其父母中未发现该位点的变异。
方法：对症治疗包括口服泼尼松（12.5mg/d）和补铁，并且在孩子中不再观察到重复感染。在膝关节中发现疼痛和活动受限。治疗方案调整为口服泼尼松（12.5mg/剂，2剂/天）并皮下注射rhTNFR：Fc（12.5mg/周）。结果:在最后一次随访中，四肢活动正常，炎症指标降低或在正常范围内。泼尼松剂量降至7.5mg/d,而rhTNFR:Fc的剂量没有改变。
结论：我们发现了一种新的致病性HA20突变。在这篇文章中,对1例患者的临床表现和这种新型疾病的新来源进行了深入分析，这可能会提高我们对这种疾病的认识。
