提高对单基因遗传自身炎症性疾病的认识

Raising awareness on monogenic autoinflammatory diseases

1999年始提出了自身炎症性疾病(AIDs)的概念,其主要为基因异常导致的单基因疾病,符合孟德尔遗传规律;到目前为止,已有20多种单基因AIDs被认识。其临床主要表现包括发热、皮疹、浆膜炎、关节炎、脑膜炎和葡萄膜炎,也常伴有淋巴结肿大和脾肿大;几乎所有患儿均存在炎症标记物增加,如白细胞、血小板、C反应蛋白(CRP)、红细胞沉降率(ESR)。当患儿出现上述临床表现,无法用另一种原因解释时(如感染或恶性肿瘤),应怀疑AIDs的可能,应尽可能进行基因检测以明确诊断。值得注意的是,同一种基因突变可以引起不同临床表型;另一方面,同一种临床表型可以由多个不同的基因突变所致。对基因检测结果的解读要基于一定遗传学知识基础,密切结合临床表型,特别是对于一些在人群中发生率很高的变异更要细心分析。

The term autoinflammatory diseases （AIDs） was proposed in 1999 to describe a group of disorders of the innate immune system characterized by recurrent episodes of inflammation without a known origin, which are frequently caused by genetic mutations in genes encoding proteins involved in the pathways of the inflammation, and follow Mendelian inheritance. At present more than 20 monogenic AIDs have been reported, of which clinical features include recurrent fever,rashes, serositis, myalgia, arthritis, meningitis, uveitis, lymphadenopathy and splenomegaly. Inflammatory markers such as leucocyte count, erythrocyte sedimentation rate （ESR） and C-reactive protein （CRP） are almost elevated in all AIDs patients. AIDs should be suspected and genetic testing should be performed in specialized laboratories when a child is presented with the above clinical manifestation that cannot be explained by other reasons （such as infection or malignant tumor）. It is noteworthy that mutation in a gene could cause different clinical phenotypes, on the other hand, a clinical phenotype could be caused by several different genes. The interpretation of gene results should be based on genetic knowledge, combined closely with clinical phenotypes, especially for some mutations with high prevalence in the population.